Biomedical subjects

Johan Garssen

Publications and source records attributed to Johan Garssen.

At least 19 recordsLinked to original sources

PubMed2025

Human milk oligosaccharides and polyphenols: Mechanisms, effects, and applications in allergies.

Human milk offers the best nutrition to the infant, which is crucial for the child's proper development and health status across the lifespan. Besides providing the substances optimally supplying the baby with energy and building materials, breast milk contains several immunometabolically active components. Those include molecules fully de novo synthesized by the mother, such as human milk oligosaccharides (HMO), and substances of nonhuman origin, transferred to the infant through mother's milk, such as dietary plant polyphenols. In this review, we outline the basic biology of HMO and polyphenols and deeply characterize their effects on the development of allergic disorders on the basis of available literature reporting data from in vitro, animal, and human studies. Further, we review the abundance of HMO and polyphenols, commonly present in mother's milk, and their mutual interactions in the context of the mechanisms underlying predisposition to, or protection against, the development of allergies. Finally, we discuss the potential of HMO and polyphenols in allergy prevention and therapy.

Humans↗

PubMed2006

A specific prebiotic oligosaccharide mixture stimulates delayed-type hypersensitivity in a murine influenza vaccination model.

Analogous to reported immunomodulatory effects of probiotics, this study was performed to analyse the immunomodulatory properties of prebiotic oligosaccharides that share chemical characteristics with human milk oligosaccharides. A mixture containing galacto- and fructo-oligosaccharides (GOS/FOS; ratio 9:1) was tested at dietary doses between 1% and 10% (w/w of total diet) in an influenza vaccination model, using 10 C56BL/6JolaHsd mice per group. The modulation of vaccine specific delayed-type hypersensitivity (DTH) responses was studied as a marker of T-helper 1 (Th1) immunity, as well as other immune parameters. GOS/FOS enhanced DTH responses dose-dependently (optimum at 5% w/w of total diet; 41.4+/-14.1% increased compared to controls, p<0.05). No significant changes were detected on splenocyte proliferation or vaccine-specific antibody concentrations. Simultaneously, GOS/FOS dose-dependently increased the proportion of faecal bifidobacteria and lactobacilli (maximal effect at 10% w/w of total diet; 16.8+/-2.4% and 5.8+/-1.3% increased compared to controls respectively, p<0.01 for both parameters). In a comparative experiment, GOS/FOS and FOS/inulin (both at 2% w/w of total diet) induced similar significant effects on the gut microbiota. In contrast to GOS/FOS, FOS/inulin did not enhance DTH responses, indicating that an increase in the proportions of bifidobacteria and lactobacilli is not sufficient for an immunomodulatory effect in this model. The use of GOS/FOS in dietary products might provide an opportunity to stimulate the adaptive immune response in a Th1-direction and subsequently inhibit infections and Th2-related immune disorders in humans, for instance allergies. Clinical studies are being performed to confirm this.

Animals↗

PubMed2006

Oral administration of the NADPH-oxidase inhibitor apocynin partially restores diminished cartilage proteoglycan synthesis and reduces inflammation in mice.

Apocynin, an inhibitor of NADPH-oxidase, is known to partially reverse the inflammation-mediated cartilage proteoglycan synthesis in chondrocytes. More recently, it was reported that apocynin prevents cyclooxygenase (COX)-2 expression in monocytes. The present study aimed to investigate whether these in vitro features of apocynin could be confirmed in vivo. In a mouse model of zymosan-induced acute arthritis apocynin was administered orally (0, 3.2, 16 and 80 microg/ml in the drinking water) and the effects on cartilage proteoglycan synthesis were monitored. In a mouse model of zymosan-induced inflammation of the ears apocynin was administered orally (14 mg/kg/day by gavage) and the effects on ear swelling and ex vivo produced prostaglandin E2 (PGE2) by lipopolysaccharide (LPS)-stimulated blood cells were measured. In this study, ibuprofen was used as a positive control (50 mg/kg/day by gavage) and animals received vehicle as a negative control. Apocynin dose-dependently reversed the inhibition of proteoglycan synthesis in articular cartilage of the arthritic joint. A statistically significant increase in proteoglycan synthesis was found at a dose of 80 microg/ml apocynin. Apocynin did not affect the proteoglycan synthesis of the control knee joints. Apocynin significantly decreased the zymosan-induced ear swelling at 1, 2 and 4 h (hours) after zymosan injection versus the vehicle treated group at 14 mg/kg/day. The ex vivo production of PGE2 by LPS-stimulated blood cells was significantly decreased after in vivo apocynin treatment. Ibuprofen decreased ear swelling at the same time-points as apocynin and inhibited the ex vivo produced PGE2. In conclusion, the present study confirmed two important features of apocynin in vivo: (1) oral administration of apocynin can partially reverse the inflammation-induced inhibition of cartilage proteoglycan synthesis, and (2) oral administration of apocynin has COX inhibitory effects similar to the non-steroidal anti-inflammatory drug (NSAID) ibuprofen. Therefore, apocynin might be of potential use during the treatment of chronic inflammatory joint diseases like osteoarthritis or rheumatoid arthritis.

Acetophenones↗

PubMed2006

Selective inhibition of COX-2 by a standardized CO2 extract of Humulus lupulus in vitro and its activity in a mouse model of zymosan-induced arthritis.

A standardized CO(2) extract from Humulus lupulus L. (hop extract) was investigated for its selective COX-1/2 inhibitory properties. An in vitro model of inflammation using lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (PBMC) was used as a model to investigate the effect of hop extract on PGE(2) production. COX-1/2 selective inhibition by the hop extract was investigated in a COX-1 whole blood assay (WBA) and a COX-2 WBA. To evaluate the in vivo activity of hop extract, it was administered orally to C57BL/6 mice in which inflammation of the right joint was induced by injecting zymosan intra-articularly. Ex vivo PGE(2) production of LPS-stimulated blood cells was determined. Also, the effect of hop extract on healthy and arthritic cartilage was investigated as well as effects on inflammatory joint swelling. Hop extract inhibited PGE(2) production by LPS-stimulated PBMC without compromising the metabolic activity of these cells. Furthermore, hop extract showed a decline in PGE(2) production in the COX-2 whole blood assay (WBA) with an IC(50) of 20.4 microg/mL, while in the COX-1 WBA no inhibition of PGE(2) production was observed. This indicates a COX-2 selective inhibition. The COX-1 inhibitor SC-560 inhibited PGE(2) production in the COX-1 WBA but not in the COX-2 WBA. At 2 microM, celecoxib inhibited PGE(2) production in the COX-2 WBA by 92 % and in the COX-1 WBA by 50 %. When hop extract was administered orally to C57BL/6 mice in which joint inflammation was induced with zymosan, PGE(2) production in ex vivo LPS-stimulated whole blood was significantly decreased by 24 %, suggesting that hop extract becomes bioavailable. Furthermore, oral administration of hop extract showed no negative or positive effects on healthy cartilage proteoglycan synthesis, or on zymosan-induced arthritic cartilage proteoglycan synthesis. However, no effect of oral administration of 1.25 mg hop extract daily was observed on joint swelling. In conclusion, this standardized CO(2) extract of Humulus lupulus could be a useful agent for intervention strategies targeting inflammatory disorders and/or inflammatory pain.

Administration, Oral↗

PubMed2005

Selective COX-2 inhibition by a Pterocarpus marsupium extract characterized by pterostilbene, and its activity in healthy human volunteers.

In this study, an extract of Pterocarpus marsupium Roxb. containing pterostilbene has been evaluated for its PGE2-inhibitory activity in LPS-stimulated PBMC. In addition, the COX-1/2 selective inhibitory activity of P. marsupium (PM) extract was investigated. Biological activity, as well as safety of PM extract was evaluated in healthy human volunteers. PM extract, pterostilbene and resveratrol inhibited PGE2 production from LPS-stimulated human peripheral blood mononuclear cells (PBMC) with IC50 values of 3.2 +/- 1.3 microg/mL, 1.0 +/- 0.6 microM and 3.2 +/- 1.4 microM, respectively. When pterostilbene content of PM extract is calculated, PGE2 production inhibition of PM extract is comparable to PGE2 production inhibition of purified pterostilbene. Furthermore, in a COX-1 whole blood assay (WBA) PM extract was not effective while in a COX-2 WBA, PM extract decreased PGE2 production indicating COX-2 specific inhibition. In healthy human volunteers, the oral use of 450 mg PM extract did not decrease PGE2 production ex vivo in a WBA. Pterostilbene levels in serum were increased, but were 5-fold lower than the observed IC50 for PGE2 inhibition in LPS-stimulated PBMC. No changes from base-line of the safety parameters were observed and no extract-related adverse events occurred during the study. In conclusion, this is the first study to describe the selective COX-2 inhibitory activity of a Pterocarpus marsupium extract. Moreover, the PGE2 inhibitory activity of PM extract was related to its pterostilbene content. In humans, 450 mg PM extract resulted in elevated pterostilbene levels in serum, which were below the active concentration observed in vitro. In addition, short-term supplementation of 450 mg PM extract is considered to be a safe dose based on the long history of use, the absence of abnormal blood cell counts and blood chemistry values and the absence of extract-related adverse events. This strongly argues for a dose-finding study of PM extract in humans to corroborate the in vitro observed inhibitory activity on PGE2 production in order to resolve the potential use of PM extract in inflammatory disorders and/or inflammatory pain.

Administration, Oral↗

PubMed2005

Galacto-oligosaccharides and long-chain fructo-oligosaccharides as prebiotics in infant formulas: a review.

UNLABELLED: The present review summarizes clinical and experimental data concerning the possible effects of a prebiotic mixture of short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides. The results from several studies, made up of over 400 preterm and term infants, clearly demonstrate that the prebiotic mixture under examination specifically stimulates the growth of bifidobacteria and lactobacilli and reduces the growth of pathogens. As a consequence of the changed intestinal flora by the dietary galacto-oligosaccharides and fructo-oligosaccharides, the faecal pH values and the short-chain fatty acid pattern were similar to those found in breastfed infants. In addition, the stool consistency was the same as in breastfed infants. In vitro experiments have demonstrated that the specific short-chain fatty acid pattern, at a pH similar to that found in faecal samples of breastfed infants, reduces the growth of pathogens in a dose-dependent manner but does not influence the growth of bifidobacteria and lactobacilli. In an animal vaccination model, the prebiotic mixture improved the response to vaccination. In an allergy model (sensitization by ovalbumin), the allergic reaction was reduced by the prebiotic mixture. The data obtained from animal experiments are in agreement with preliminary data from clinical trials which indicate a reduced allergic response (reduced plasma IgE/IgG4 ratio) and reduced episodes of upper airway infection during the first year of life. CONCLUSION: Experimental evidence demonstrates that the prebiotic mixture employed in these studies modulates the intestinal flora and modulates the immune system as human milk does. There are sufficient experimental data to put forward the hypothesis that substances like the prebiotic mixture under study will substantially contribute to the improvement of the protective properties of infant formulas.

Feces↗

PubMed2004

Release kinetics and cell trafficking in relation to bacterial growth explain the time course of blood neutrophils and monocytes during primary Salmonella infection.

Granulocytes and neutrophils are predominantly responding cells during the early phase of infection of rats with Salmonella. We propose mathematical and experimental models of the kinetics of neutrophil and monocyte responses in Salmonella infection via the oral route. Using the models, we estimate that approximately 1 in 500 inoculated Salmonella cells actually infected the rat and multiplied with a doubling time of 5 h in Peyer's patches, reaching a maximum of approximately 10(6) c.f.u./g. In low-dose infection, neutrophil and monocyte responses are delayed, but further resemble the responses in high-dose infection. Important processes influencing neutrophil and monocyte recruitment are: massive migration into the infected tissue, and non-linear release kinetics of neutrophils and monocytes from the bone marrow. In conclusion, we can predict time series of neutrophil and monocyte responses in low-dose and high-dose experimental infection via the oral route.

Animals↗

PubMed2004

Decreased pro-inflammatory cytokine production by LPS-stimulated PBMC upon in vitro incubation with the flavonoids apigenin, luteolin or chrysin, due to selective elimination of monocytes/macrophages.

Apigenin and its structural analogues chrysin and luteolin were used to evaluate their capacity to inhibit the production of pro-inflammatory cytokines by lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (PBMC). Furthermore, flowcytometric analysis was performed to compare the effects of apigenin, chrysin, luteolin, quercetin and naringenin on the different cell types present in PBMC. LPS-stimulated PBMC were cultured in the presence of the flavonoids and TNFalpha, IL-1beta and IL-6 were measured in the supernatants. In parallel, metabolic activity of the PBMC was determined by measuring succinate dehydrogenase activity. Apigenin, chrysin and luteolin dose-dependently inhibited both pro-inflammatory cytokine production and metabolic activity of LPS-stimulated PBMC. With increasing concentration of apigenin, chrysin or luteolin the monocytes/macrophages disappeared as measured by flowcytometry. This also appeared to occur in the non-LPS-stimulated PBMC. At the same time there was an increase in dead cells. T- and B-lymphocytes were not affected. Quercetin and naringenin had virtually no effects on cytokines, metabolic activity or on the number of cells in the studied cell populations. In conclusion, monocytes were specifically eliminated in PBMC by apigenin, chrysin or luteolin treatment in vitro at low concentrations (around 8 microM), in which apigenin appeared to be the most potent.

Adult↗

PubMed2004

Cow's milk-specific T-cell reactivity of children with and without persistent cow's milk allergy: key role for IL-10.

BACKGROUND: The role of antigen-specific T cells in the mechanism of food allergy or maintenance of tolerance toward an innocuous antigen, such as cow's milk, is not yet fully understood. OBJECTIVE: The cow's milk-specific T-cell response of donors with various allergic backgrounds was investigated. METHODS: Cow's milk-specific T-cell clones (TCCs) were generated from the blood of children with persistent cow's milk allergy (CMA) and the blood of cow's milk-tolerant allergic and nonallergic control subjects. The TCCs were characterized by their antigen-specific proliferation, cytokine production, and activation status. RESULTS: Cow's milk-specific TCCs of children with persistent CMA were T(H)2 skewed, and the production of IL-4 and IL-13 was significantly correlated with the expression of the activation marker CD25. TCCs of the allergic control subjects were characterized by a high production of IL-10, which was positively correlated with the production of IL-4 and IFN-gamma and with the expression of CD25. TCCs derived from nonallergic control subjects had an attenuated response toward cow's milk in that they did not produce high levels of cytokines nor did they express high levels of surface markers. As in the allergic control subjects, in the nonallergic control subjects IL-10 production was positively correlated with the expression of CD25. CONCLUSION: The activation status of T cells derived from persistent donors with CMA was associated with the production of IL-4 and IL-13, whereas activated TCCs of cow's milk-tolerant control subjects were characterized by the production of IL-10 and, to a lesser extent, IFN-gamma. These findings suggest that activated CD4(+) T cells (characterized by a high CD25 expression) might contribute to the tolerogenic immune response toward an antigen, such as cow's milk, through the production of IL-10.

Adolescent↗

PubMed2004

Intraspecies variability in the dose-response relationship for Salmonella Enteritidis associated with genetic differences in cellular immune response.

To evaluate the effects of differences in host cellular immunity, we studied the dose-response relationship for infection with Salmonella enterica serovar Enteritidis (SE) in two different rat strains, skewed towards T helper 1 (Th1, Lewis rats) or T helper 2 (Th2, Brown Norway rats) immunoregulation. Rats were exposed orally to different doses of SE after overnight starvation and neutralization of gastric acid. Animals were observed for clinical signs of disease, fecal excretion and SE load in spleen and cecum, histopathology of the cecum, hematology, and cellular and humoral immune responses. Exponential dose-response models were used for binary or continuous outcomes to analyze the experimental data. Cytokine patterns, antibody isotypes, and contact hypersensitivity tests confirmed that Lewis rats are Th1 prone, whereas Brown Norway rats are Th2 prone. The probability of infection per single SE cell was approximately 100 times higher in Brown Norway rats than in Lewis rats. Cellular immune responses were more pronounced in Lewis rats but antibody responses were higher in Brown Norway rats. When infected, colonization levels and inflammation are highest in the intestinal tract of Th2 skewed rats, but systemic infection is more intense in Th1 skewed rats. Successful colonization by only one or two SE clones resulted in a marked increase of neutrophil counts by a factor of two to three in both rat strains.

Administration, Oral↗

PubMed2003

Cytokine polymorphisms play a role in susceptibility to ultraviolet B-induced modulation of immune responses after hepatitis B vaccination.

UVB exposure can alter immune responses in experimental animals and humans. In an earlier human volunteer study, we demonstrated that hepatitis B-specific humoral and cellular immunity after vaccination on average were not significantly affected by UVB exposure. However, it is known that individuals differ in their susceptibility to UVB-induced immunomodulation, and it was hypothesized that polymorphisms in specific cytokines may play a role in this susceptibility. In this respect, we previously demonstrated that immune responses after hepatitis B vaccination are influenced by the minor allelic variant of IL-1 beta in the general population. For all volunteers, single nucleotide polymorphisms were determined for the following UV response-related cytokines: IL-1 receptor antagonist (+2018), IL-1 alpha (+4845), IL-1 beta (+3953), TNF-alpha (-308), and TNF-alpha (-238). Exposure to UVB significantly suppressed Ab responses to hepatitis B in individuals with the minor variant for the IL-1 beta polymorphism. Increased minimal erythema dose values (just perceptible), which resulted in higher absolute UVB exposures, were observed in the same individuals. There were no associations observed between UVB-induced immunomodulation and the other cytokine polymorphisms examined. This study indicates that individual susceptibility to UVB radiation needs to be considered when studying the effects of UVB in humans.

Adult↗

PubMed2003

Functional CD25- and CD25+ mucosal regulatory T cells are induced in gut-draining lymphoid tissue within 48 h after oral antigen application.

Oral antigen application induces tolerance, leading to suppression of a subsequent systemic challenge with this antigen. The suppression is mediated by mucosal regulatory T (Tr) cells that may differentiate from naive peripheral T cells in the gut-draining lymphoid tissue. However, little is known about the initial steps of this differentiation process. In this study we show that 48 h after oral OVA treatment, antigen-specific T cells in mesenteric lymph nodes (MLN) and Peyer's Patches (PP) were activated and had divided up to four times. The first division was already seen in PP after 24 h. Analysis of surface marker expression and cytokine secretion of the dividing antigen-specific T cells revealed that they sequentially obtained an activation- and memory-like phenotype. These cells secreted IL-2 in most stages of division but only transiently IFN-gamma whereas no IL-4 or IL-10 secretion was detected. Remarkably, 48 h after antigen application, isolated dividing cells were suppressive, as they transferred tolerance to naive mice. Even though CD25 was expressed heterogeneously, both CD25(+) and CD25(-) OVA-specific T cells from MLN could transfer tolerance. Together these findings show that differentiation of functional Tr cells occurs in the MLN and PP within 2 days after antigen ingestion and involves the generation of CD25(+) and CD25(-) antigen-specific T cells.

ADP-ribosyl Cyclase↗

PubMed2003

Ultraviolet B radiation induces upregulation of calcitonin gene-related peptide levels in human Finn chamber skin samples.

One of the neuropeptides that plays a role in UVB-induced immunomodulation is calcitonin gene-related peptide (CGRP), as demonstrated in several animal studies. CGRP can be detected in human skin, but effects of UVB exposure on CGRP levels in human skin are not known. We determined CGRP levels in human Finn chamber skin samples of 15 UVB-irradiated and 10 control volunteers. Filter samples were collected prior to and immediately after a UVB exposure protocol (5 consecutive days, with one personally determined minimal erythema dose (MED(jp)) per day). CGRP levels in filter samples were determined using a commercially available radioimmunoassay kit. CGRP could be detected in the filter samples and volunteers showed statistically significantly increased levels after UVB exposure. In addition, the CGRP levels of UVB-exposed volunteers were positively correlated with the dose of UVB in J/m(2) that they received on 5 consecutive days. In other words, higher UVB doses resulted in higher CGRP levels. In summary, CGRP, a mediator in UVB-induced immunomodulation, could be detected in human Finn chamber skin samples, and was significantly increased after UVB exposure. The CGRP level appeared to depend on the amount of UVB the volunteers received.

Calcitonin Gene-Related Peptide↗

PubMed2003

Association of transcription-coupled repair but not global genome repair with ultraviolet-B-induced Langerhans cell depletion and local immunosuppression.

Exposure to ultraviolet-B radiation impairs cellular immune responses. This immunosuppression seems to be associated with Langerhans cell migration. DNA damage appears to play a key role because enhanced nucleotide excision repair, a pathway essential for elimination of ultraviolet-B-induced DNA lesions, strongly counteracts immunosuppression. To determine the effect of DNA repair on ultraviolet-B-induced local immunosuppression and Langerhans cell disappearance, three mouse strains carrying different defects in nucleotide excision repair were compared. XPC mice, which were defective in global genome repair, were as sensitive to ultraviolet-B-induced local suppression of contact hypersensitivity to picryl chloride as their wild-type littermates. CSB mice, defective in transcription-coupled repair, were far more sensitive for immunosuppression as were XPA mice, defective in both transcription-coupled repair and global genome repair. Only a moderate depletion of Langerhans cells was observed in XPC mice and wild-type littermates. Ultraviolet-B-induced Langerhans cell depletion was enhanced in CSB and XPA mice. Hence, the major conclusion is that local immunosuppression is only affected when transcription-coupled DNA repair is impaired. Furthermore, a defect in transcription-coupled repair was linked to enhanced ultraviolet-B-induced Langerhans cell depletion. In combination with earlier experiments, it can be concluded that Langerhans cell disappearance is related to ultraviolet-B-induced local but not to systemic immunosuppression.

Animals↗

PubMed2003

Transforming growth factor-beta inhibits human antigen-specific CD4+ T cell proliferation without modulating the cytokine response.

Transforming growth factor (TGF)-beta has been demonstrated to play a key role in the regulation of the immune response, mainly by its suppressive function towards cells of the immune system. In humans, the effect of TGF-beta on antigen-specific established memory T cells has not been investigated yet. In this study antigen-specific CD4(+) T cell clones (TCC) were used to determine the effect of TGF-beta on antigen-specific proliferation, the activation status of the T cells and their cytokine production. This study demonstrates that TGF-beta is an adequate suppressor of antigen-specific T cell proliferation, by reducing the cell-cycle rate rather than induction of apoptosis. Addition of TGF-beta resulted in increased CD69 expression and decreased CD25 expression on T cells, indicating that TGF-beta is able to modulate the activation status of in vivo differentiated T cells. On the contrary, the antigen-specific cytokine production was not affected by TGF-beta. Although TGF-beta was suppressive towards the majority of the T cells, insensitivity of a few TCC towards TGF-beta was also observed. This could not be correlated to differential expression of TGF-beta signaling molecules such as Smad3, Smad7, SARA (Smad anchor for receptor activation) and Hgs (hepatocyte growth factor-regulated tyrosine kinase substrate). In summary, TGF-beta has a pronounced inhibitory effect on antigen-specific T cell proliferation without modulating their cytokine production.

Animals↗

PubMed2003

Epidermal cis-urocanic acid levels correlate with lower specific cellular immune responses after hepatitis B vaccination of ultraviolet B-exposed humans.

Urocanic acid (UCA) is a major UV-absorbing chromophore in the epidermis and has been suggested to act as one of the initiators of UV-induced immunosuppression. cis-UCA, the isomer from UCA that is formed upon UV exposure, has been shown to impair some cellular immune responses. cis-UCA levels were determined in a study in which the influence of ultraviolet B (UVB) exposure on immune responses after hepatitis B vaccination in human volunteers was established. A significant increase in cis-UCA levels was found in the skin of UVB-exposed volunteers compared with controls. cis-UCA levels, calculated as the percentage of the total UCA amount, in UVB-exposed volunteers correlated significantly with the cumulative UVB dose received in 5 consecutive days, i.e. the higher the UVB dose (J/m2), the higher the cis-UCA levels (until a cis-UCA plateau was reached in the so-called photostationary state). Correlations between skin cis-UCA levels and immune responses were determined, and they revealed no statistically significant correlations among lymphocyte proliferation responses after either mitogenic stimulation or stimulation with recall antigens. No correlation was found between cis-UCA levels and hepatitis B-specific antibody titers. However, we found a statistically significant negative correlation between cis-UCA levels and hepatitis B-specific lymphocyte proliferation responses when volunteers were irradiated with UVB before hepatitis B vaccination. In other words, volunteers with high cis-UCA levels caused by UVB exposure showed lower cellular immune responses against hepatitis B antigen after hepatitis B vaccination.

Adult↗

PubMed2002

IL-1beta gene polymorphisms influence hepatitis B vaccination.

Considerable variability exists in the vaccine response to hepatitis B with 5-10% of healthy young adults demonstrating no or inadequate responses following a standard vaccination schedule. As the interleukin-1beta (IL-1beta) cytokine has been shown to be important in the development of immune responses, we determined whether vaccine efficacy is influenced by genetic polymorphisms associated with IL-1beta expression. Ninety-two healthy individuals who were negative for antibodies to hepatitis B antigen (anti-HBs) were vaccinated against hepatitis B according to a standardized schedule. At selected times, antibody titers and lymphoproliferative capacity to hepatitis B surface antigen (HBsAg) were determined. DNA genotyping for IL-1beta polymorphisms using a polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) technique demonstrated that both the anti-HBs titer and the T-cell lymphoproliferative response to HBsAg are significantly increased in individuals possessing the IL-1beta (+3953) minor allelic variant.

Adult↗

PubMed2002

Immunoglobulin-free light chains elicit immediate hypersensitivity-like responses.

Immunoglobulin (Ig)-free light chains IgLC are present in serum and their production is augmented under pathological conditions such as multiple sclerosis, rheumatoid arthritis and neurological disorders. Until now, no (patho)physiological function has been ascribed to circulating Ig light chains. Here we show that IgLCs can confer mast cell dependent hypersensitivity in mice. Antigenic stimulation results in plasma extravasation, cutaneous swelling and mast-cell degranulation. We show that IgLCs have a crucial role in development of contact sensitivity, which could be completely prevented by a novel IgLC antagonist. Although IgE and IgG(1) are central to the induction of immediate hypersensitivity reactions, our results show that IgLCs have similar activity. IgLCs may therefore be a novel factor in the humoral immune response to antigen exposure. Our findings open new avenues in investigating the pathogenesis of autoimmune diseases and their treatments.

Animals↗