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Biomedical subjects

Mario Delgado

Publications and source records attributed to Mario Delgado.

At least 55 records · Page 3Linked to original sources
PubMed2003

Inhibition of interferon (IFN) gamma-induced Jak-STAT1 activation in microglia by vasoactive intestinal peptide: inhibitory effect on CD40, IFN-induced protein-10, and inducible nitric-oxide synthase expression.

Interferon (IFN)-gamma is one of the most important microglia stimulators in vivo participating in inflammation and Th1 activation/differentiation. IFN-gamma-mediated signaling involves the activation of the Jak/STAT1 pathway. The neuropeptides vasoactive intestinal peptide (VIP) and the pituitary adenylate cyclase activating polypeptide (PACAP) are two potent microglia-deactivating factors that inhibit the production of proinflammatory mediators in vitro and in vivo. The present study investigated the molecular mechanisms involved in the VIP/PACAP regulation of several IFN-gamma-induced microglia-derived factors, including IFN-gamma-inducible protein-10 (IP-10), inducible nitric-oxide synthase (iNOS), and CD40. The results indicate that VIP/PACAP inhibit Jak1-2 and STAT1 phosphorylation, and the binding of activated STAT1 to the IFN-gamma activated site motif in the IFN regulatory factor-1 and CD40 promoter and to the IFN-stimulated response element motif of the IP-10 promoter. Through its effect in the IFN-gamma-induced Jak/STAT1 pathway, VIP and PACAP are able to control the gene expression of IP-10, CD40, and iNOS, three microglia-derived mediators that play an essential role in several pathologies, i.e. inflammation and autoimmune disorders. The effects of VIP/PACAP are mediated through the specific receptor VPAC1 and the cAMP/protein kinase A transduction pathway. Because IFN-gamma is a major stimulator of innate and adaptive immune responses in vivo, the down-regulation of IFN-gamma-induced gene expression by VIP and PACAP could represent a significant element in the regulation of the inflammatory response in the central nervous system by endogenous neuropeptides.

Amino Acid Motifs↗
PubMed2003

Vasoactive intestinal peptide inhibits IL-8 production in human monocytes by downregulating nuclear factor kappaB-dependent transcriptional activity.

Although interleukin-8 (IL-8) is a chemokine that plays a beneficial and central role in the inflammatory response, hematopoiesis, and angiogenesis, excessive IL-8 production can be deleterious to the host, and its selective inhibition represents an important therapeutic goal. Vasoactive intestinal peptide (VIP) is a neuropeptide that acts as a potent anti-inflammatory agent inhibiting the function of activated macrophages/monocytes. The present study reports the effect of VIP on IL-8 production by stimulated human THP1 monocytes. VIP inhibits IL-8 production in a dose- and time-dependent manner at the mRNA level. VIP seems to act by inhibiting the NF-kappaB-dependent IL-8 gene activation. The specific VPAC1 receptor mediates the inhibitory effect of VIP. Two transduction pathways appear to be involved, a major cAMP-independent pathway that preferentially blocks nuclear translocation of NF-kappaB and its binding to the kappaB site of the IL-8 promoter, and a cAMP-dependent pathway that inhibits the activation and binding to the IL-8 promoter of both CREB-binding protein (CBP) and TATA box-binding protein (TBP), two transcriptional cofactors strictly required for the transactivating activity of NF-kappaB. These findings support the proposed role of VIP as a key endogenous anti-inflammatory agent and describe a novel mechanism, i.e., the inhibition of the production of monocyte-derived IL-8, and are of obvious physiological significance, because VIP, through the inhibition of IL-8 production, could reduce the monocyte-induced neutrophil chemotaxis/infiltration, an important event in the pathogenesis of several inflammatory and autoimmune disorders.

Down-Regulation↗
PubMed2003

Neuroprotective effect of vasoactive intestinal peptide (VIP) in a mouse model of Parkinson's disease by blocking microglial activation.

Parkinson's disease (PD) is a common neurodegenerative disorder with no effective protective treatment, characterized by a massive degeneration of dopaminergic neurons in the substantia nigra (SNpc) and the subsequent loss of their projecting nerve fibers in the striatum. To elucidate PD pathogenic factors, and thus to develop therapeutic strategies, a murine PD model based on the administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been used extensively. It has been demonstrated that activated microglia cells actively participate in the pathogenesis of MPTP-induced PD through the release of cytotoxic factors. Because current treatments for PD are not effective, considerable research focused lately on a number of regulatory molecules termed microglia-deactivating factors. Vasoactive intestinal peptide (VIP), a neuropeptide with a potent anti-inflammatory effect, has been found to be protective in several inflammatory disorders. This study investigates the putative protective effect of VIP in the MPTP model for PD. VIP treatment significantly decreases MPTP-induced dopaminergic neuronal loss in SNpc and nigrostriatal nerve-fiber loss. VIP prevents MPTP-induced activation of microglia in SNpc and striatum and the expression of the cytotoxic mediators, iNOS, interleukin 1beta, and numor necrosis factor alpha. VIP emerges as a potential valuable neuroprotective agent for the treatment of pathologic conditions in the central nervous system, such as PD, where inflammation-induced neurodegeneration occurs.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2003

Vasoactive intestinal peptide inhibits IL-8 production in human monocytes.

Vasoactive intestinal peptide (VIP), a neuropeptide present in the lymphoid microenvironment, acts as a potent anti-inflammatory agent that inhibits the function of activated macrophages. VIP was shown to inhibit IL-6, TNFalpha, IL-12, chemokine, and nitric oxide production in endotoxin-activated macrophages. The present study reports the effect of VIP on IL-8 production by stimulated human monocytes. VIP inhibits IL-8 production in a dose- and time-dependent manner at the mRNA level. The specific VPAC1 receptor mediates the inhibitory effect of VIP. Two transduction pathways appear to be involved, a major cAMP-independent pathway and a secondary cAMP-dependent pathway. Of obvious physiological significance is the fact that VIP, presumably through the inhibition of IL-8 production, dramatically reduces the monocyte-induced neutrophil chemotaxis, an important event in the pathogenesis of several inflammatory and autoimmune disorders. These findings support the proposed role of VIP as a key endogenous anti-inflammatory agent and describe a novel mechanism, i.e., the inhibition of the production of monocyte-derived IL-8.

Anti-Inflammatory Agents↗
PubMed2003

Therapeutic effects of vasoactive intestinal peptide in the trinitrobenzene sulfonic acid mice model of Crohn's disease.

BACKGROUND & AIMS: Crohn's disease (CD) is a chronic debilitating disease of unknown etiology that is characterized by severe inflammation of the colon. Vasoactive intestinal peptide (VIP) has recently emerged as a promising candidate for treatment of inflammatory Th1-driven diseases. We studied the effect of VIP in trinitrobenzene sulfonic acid (TNBS)-induced colitis, which has clinical and molecular features in common with CD. METHODS: A 3-mg enema of TNBS was given to BALB/c mice, and VIP (1 nmol) was given either as a single dose at 12 hours or every other day. Weight loss, histopathology, and chemokine and cytokine levels in serum and colon extracts were assessed. VIP was also tested given 5 days after the onset of TNBS-induced colitis, and its effect was analyzed given a second dose of TNBS. RESULTS: Treatment with VIP reduced the clinical and histopathologic severity of TNBS-induced colitis, abrogating body weight loss, diarrhea, and macroscopic and microscopic intestinal inflammation. The therapeutic effects of VIP were associated with down-regulation of both inflammatory and Th1-driven autoimmune responses, including tumor necrosis factor alpha, interleukin 1, and interleukin 6 in colon extracts and serum as well as interferon gamma by splenic and lamina propria CD4(+) T cells. VIP reduced disease severity when given after disease onset and dramatically reduced disease recurrence given a second dose of TNBS. CONCLUSIONS: Our data suggest that VIP has beneficial prophylactic and therapeutic effects in TNBS-induced colitis and is a promising candidate to test for potential benefits in CD.

Animals↗
PubMed2003

PACAP in immunity and inflammation.

The pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide belonging to the VIP/secretin/glucagon family of peptides, produced by the lymphoid cells, which exerts a wide spectrum of immunological functions controlling the homeostasis of immune system through different receptors expressed in various immunocompetent cells. In the last decade, PACAP has been clearly identified as a potent anti-inflammatory factor that exerts its function by regulating the production of both anti- and proinflammatory mediators. In this sense, PACAP prevents death by septic shock, an acute inflammatory disease with a high mortality. In addition, PACAP regulates the expression of costimulatory molecules, inasmuch as this related to the modulation in the shift from Th1 towards Th2 differentiation. We recently reported that PACAP prevents the deleterious effects of arthritis by downregulating both inflammatory and autoimmune components of the disease. Therefore, PACAP and analogs have been proposed as very promising candidates, alternative to other existing treatments, for treating acute and chronic inflammatory and autoimmune diseases, such as septic shock, arthritis, multiple sclerosis, Crohn's disease, or autoimmune diabetes.

Animals↗
PubMed2003

Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit the production of inflammatory mediators by activated microglia.

Microglia play a central role in the regulation of immune and inflammatory activities, as well as tissue remodeling in the central nervous system. However, activation of microglia is a histopathological hallmark of several neurodegenerative diseases. Pathological microglial activation is believed to contribute to progressive damage in neurodegenerative diseases through the release of proinflammatory and/or cytotoxic factors, including tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, IL-12, and nitric oxide (NO). Hence, it is important to unravel mechanisms regulating microglia activation of inflamed brain parenchyma to provide insights into efficient therapeutic intervention. This study examines the role of two anti-inflammatory neuropeptides, the vasoactive intestinal peptide (VIP) and the pituitary adenylate cyclase-activating polypeptide (PACAP) on the production of various proinflammatory factors by endotoxin-stimulated microglia. VIP and PACAP inhibit TNF-alpha, IL-1beta, IL-6, and NO production by lipopolysaccharide (LPS)-activated microglia. The specific type 1 VIP receptor mediates the inhibitory effect of VIP/PACAP, and cyclic adenosine monophosphate is the major, second messenger involved. VIP and PACAP regulate the production of these proinflammatory factors at a transcriptional level by inhibiting p65 nuclear translocation and nuclear factor-kappaB-DNA binding. This effect is mediated, as neuropeptides stabilize the inhibitor IkappaB by inhibiting LPS-induced IkappaB-kinase activity. Therefore, the inhibitory effects on the production of proinflammatory mediators define VIP and PACAP as "microglia-deactivating factors" with significant, therapeutical potential for inflammatory/degenerative brain disorders.

Animals↗
PubMed2003

The neuropeptides VIP/PACAP and T cells: inhibitors or activators?

The structurally related neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) are released within the lymphoid organs following antigenic stimulation, and modulate the function of inflammatory cells through specific receptors. In activated macrophages, VIP and PACAP inhibit the expression at both mRNA and protein level of pro-inflammatory cytokines and chemokines, through effects on de novo expression or nuclear translocation of a number of transcription factors, i.e. NFkB, CREB, c-Jun, JunB, and IRF-1. In addition, VIP and PACAP promote Th2-type, and inhibit Th1-type responses in vivo and in vitro, through several mechanisms, including preferential survival of Th2 effectors and subsequent generation of Th2 memory cells. The function of VIP/PACAP as "macrophage deactivating factors" appears to be responsible for their protective effect in vivo in models of septic shock. Both deactivation of macrophages and inhibition of Th1-type responses appear to be responsible for the beneficial effect of VIP/PACAP in models of Th1-type autoimmune diseases such as rheumatoid arthritis.

Animals↗
PubMed2002

Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit CBP-NF-kappaB interaction in activated microglia.

The vasoactive intestinal peptide (VIP) and the pituitary adenylate cyclase-activating polypeptide (PACAP), two immunomodulatory neuropeptides, act as anti-inflammatory factors for activated microglia, by inhibiting the production of pro-inflammatory factors, mainly mediated through the inhibition of NF-kappaB nuclear translocation and DNA binding. An additional regulatory element in the NF-kappaB transcriptional activity is the coactivator CBP, which links p65 with components of the basal transcriptional machinery. The present report demonstrates that VIP and PACAP inhibit the formation of p65/CBP complexes and that this event is directly related to the neuropeptide inhibition of NF-kappaB transcriptional activity. Since CBP is in limiting amounts in the nucleus and is capable of interacting with several transcriptional factors, competition for CBP provides another mechanism for transcriptional regulation. VIP and PACAP increase CBP-binding to CREB, replacing p65/CBP with CREB/CBP complexes in activated microglia. This is due to VIP/PACAP-induced increases in CREB phosphorylation/activation and is mediated through the specific VPAC1 receptor and the cAMP/PKA pathway. The VIP/PACAP interference with the p65/CBP interaction in activated microglia may represent a significant element in the regulation of the inflammatory response in the CNS by the endogenous neuropeptides.

Active Transport, Cell Nucleus↗
PubMed2002

Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide promote in vivo generation of memory Th2 cells.

Functionally active effector T cells are generated through clonal expansion. Most effector T cells are later eliminated, whereas a small number survive and differentiate into memory T cells. The mechanisms by which some effector T cells escape apoptosis and become memory T cells are not understood. Neuropeptides such as the vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) inhibit antigen-induced apoptosis of CD4 T cells. By using an in vivo long-term experimental model, in which CD4 T cells from TRC-transgenic mice were transferred into hosts, we demonstrate that VIP and PACAP induce the survival and/or generation of antigen-specific CD4 T cells with a memory Th2 phenotype. This was confirmed by the fact that transgenic CD4 T cells were recovered only from mice that received Th2, but not Th1 effector cells, in the presence of VIP or PACAP. In vitro, VIP/PACAP support the survival of Th2, but not Th1, cell lines through an inhibition of antigen-induced apoptosis. The role of neuropeptides in the biased development of Th2 memory cells is particularly relevant in view of the immune deviation existing in immune-privileged sites such as the brain and eye, where Th2, but not Th1, responses occur in nonpathological conditions.

Animals↗
PubMed2002

Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit the MEKK1/MEK4/JNK signaling pathway in endotoxin-activated microglia.

The vasoactive intestinal peptide (VIP) and the pituitary adenylate cyclase-activating polypeptide (PACAP), two immunomodulatory neuropeptides, act as anti-inflammatory factors for activated microglia, by inhibiting the production of proinflammatory factors. In the present study the effects of VIP/PACAP on the MEKK1/MEK4/JNK transduction pathway and on the subsequent changes in Jun family members, a transduction pathway clearly involved in the activation of microglia cells were examined. VIP/PACAP inhibit MEKK1 activity and the subsequent phosphorylations of MEK4, JNK, and c-Jun, which result in a decrease in the AP-1 binding and a marked change in the composition of AP-1 complexes from c-Jun/c-Fos to JunB/c-Fos. Furthermore, VIP stimulates JunB production in LPS-stimulated microglia. Both inhibition of the MEKK1/MEK4/JNK pathway, leading to a reduction in phosphorylated c-Jun, and the stimulation of JunB are mediated through the specific VPAC1 receptor and cAMP/PKA pathway. The VIP/PACAP interference with the stress-induced SAPK/JNK pathway in activated microglia may represent a significant element in the regulation of inflammatory response in the CNS by endogenous neuropeptides.

Animals↗
PubMed2002

Anti-inflammatory role in septic shock of pituitary adenylate cyclase-activating polypeptide receptor.

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are two mediators synthesized by immune cells, specially under inflammatory and antigen stimulation conditions. Reports have shown that neuropeptides attenuate the deleterious consequences of septic shock both by down-regulating the production of proinflammatory mediators and by stimulating the production of anti-inflammatory cytokines by activated macrophages. In this study, we used a knockout for the PACAP receptor (PAC1(-/-)) to demonstrate an important protective role for PAC1 receptor in endotoxic shock. Moreover, our results indicate that PAC1 receptor acts in vivo as an anti-inflammatory receptor, at least in part, by attenuating lipopolysaccharide (LPS)-induced production of proinflammatory IL-6, which appears to be the main cytokine regulating the expression of the majority of the acute phase protein genes, which are an important deleterious component of septic shock. Besides, our findings point to endogenously produced VIP and PACAP as participants of the natural anti-inflammatory machinery. Because VIP and PACAP are two attractive candidates for the development of therapies against acute and chronic inflammatory diseases, septic shock, and autoimmune diseases, this paper represents a contribution to the understanding of the mechanism of action of these anti-inflammatory agents.

Animals↗
PubMed2002

Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit chemokine production in activated microglia.

Microglia react to even minor disturbances in CNS homeostasis and function as critical regulators of CNS inflammation. Activated microglia secrete inflammatory mediators such as cytokines and chemokines, which contribute to the pathophysiological changes associated with several neuroimmunologic disorders. Microglia-derived inflammatory chemokines recruit various populations of immune cells, which initiate and maintain the inflammatory response against foreign antigens. Entry and retention of activated immune cells in the CNS is a common denominator in a variety of traumatic, ischemic, and degenerative diseases. Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are two structurally related neuropeptides that function as potent anti-inflammatory factors in the periphery. Here we investigated the effects of VIP and PACAP on chemokine production by activated microglia. VIP and PACAP inhibit the expression of the microglia-derived CXC chemokines MIP-2 and KC, and of the CC chemokines MIP-1alpha, -1beta, MCP-1, and RANTES. The inhibition of chemokine gene expression correlates with an inhibitory effect of VIP/PACAP on NFkB binding. The VIP/PACAP inhibition of both chemokine production and of NFkB binding is mediated through the specific receptor VPAC1 and involves a cAMP-dependent intracellular pathway. Of biological significance is the fact that the inhibition of chemokine production by VIP/PACAP leads to a significant reduction in the chemotactic activity generated by activated microglia for peripheral leukocytes, i.e., neutrophils, macrophages, and lymphocytes. Because reduction in the number and activation of infiltrating leukocytes represents an important factor in the control of inflammation in the CNS, VIP and/or PACAP released by neurons during an inflammatory response could serve as neuronal survival factors by limiting the inflammatory process.

Animals↗
PubMed2002

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) as modulators of both innate and adaptive immunity.

The structurally related neuropeptides VIP and PACAP are released within the lymphoid organs following antigenic stimulation, and modulate the function of inflammatory cells through specific receptors. In activated macrophages, VIP and PACAP inhibit the production of pro-inflammatory agents (cytokines, chemokines, and nitric oxide), and stimulate the production of the anti-inflammatory cytokine IL-10. These events are mediated through the VIP/PACAP effects on de novo expression or nuclear translocation of several transcription factors, i.e., NFkappaB, CREB, c-Jun, JunB, and IRF-1. The in vivo administration of VIP/PACAP results in a similar pattern of cytokine and chemokine modulation, which presumably mediates the protective effect of VIP/PACAP in septic shock. In addition, VIP/PACAP reduce the expression of the co-stimulatory molecules B7.1/B7.2, and the subsequent stimulatory activity of macrophages for T-helper cells. In T-cells expressing specific VIP/PACAP receptors, VIP and PACAP inhibit the expression of FasL through effects on NFkappaB, NFAT, and Egr2/3. The reduction of FasL expression has several biological consequences: inhibition of antigen-induced cell death in CD4 T-cells, inhibition of the FasL-mediated cytotoxicity of CD8 and CD4 effectors against direct and bystander targets, and promotion of long-term memory Th2 cells, through a positive effect on the survival of Th2, but not Th1, effectors. The various biological effects of VIP and PACAP are discussed within the range of a general anti-inflammatory model.

Adjuvants, Immunologic↗
PubMed2002

Comparison of immunophenotypes in the blood of patients on continuous ambulatory peritoneal dialysis, asymptomatic and with peritonitis.

Peritonitis is a complication of continuous ambulatory peritoneal dialysis (CAPD) that often causes fibrosis. Understanding the role played by the immune system is required if we are to understand the mechanisms of defense and tissue lesion triggered by germs. We compared the characteristics of the blood immunophenotypes of patients on CAPD, with and without peritonitis. This descriptive, prospective study was carried out in the dialysis unit of San José University Hospital, a tertiary care institution in Popayán, Colombia. In blood samples from 46 patients on CAPD (26 with peritonitis and 20 without peritonitis), we used flow cytometry to measure cytokine production at the single-cell level. The diagnosis of peritonitis was made by standard clinical and laboratory criteria. We noted general clinical characteristics of the patients; percentages of lymphocytes, monocytes, neutrophils, and eosinophils; and cell counts of lymphocytes (CD4 cells, CD8 cells) and their subsets [B1, B2, and natural killer (NK) cells]. We also determined the CD4:CD8 ratio. We found significant differences in the levels of serum albumin (p < 0.001), the percentages of lymphocytes (p < 0.04) and neutrophils (p < 0.04), and the counts of B1 and B2 cells, especially in patients whose CD4:CD8 ratio was below 1.2. Those patients also had more intense CD4 lymphopenia, more CD8 cells (principally T-suppressor cells), and more expansion of NK cells. In patients on CAPD, an important immune activation and rise in the percentage of B1 cells occurs that increases with peritonitis. Among the general clinical characteristics, albumin was the only one to show a statistically significant difference between patients with and without peritonitis. An important CD4 lymphopenia occurred in patients with a CD4:CD8 ratio below 1.2.

CD4-CD8 Ratio↗
PubMed2002

Cytokines and peritonitis in continuous ambulatory peritoneal dialysis: immunodeviation and immunodeficiency.

Cytokines are soluble mediators of the immune system, which regulate the immune response to antigenic stimuli. In continuous ambulatory peritoneal dialysis (CAPD) patients with peritonitis, an inflammatory process occurs, but the patterns of cytokine secretion have not yet been clarified. We compared the characteristics of the intracellular production of cytokines and looked for the immunophenotypes T helper 1 (TH1), T helper 2 (TH2), and T helper 0 (TH0) in CAPD patients with and without peritonitis. Our descriptive, prospective study was carried out in the dialysis unit of the San José University Hospital, a tertiary health care center in Popayán, southwest Colombia. We obtained 28 peripheral blood samples from CAPD patients (8 with peritonitis and 20 without peritonitis) and processed them by flow cytometry for intracellular detection of cytokines. The peritonitis diagnosis was made based using established clinical and laboratory criteria. We measured the general clinical characteristics and percentage of intracellular production of interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-12 (IL-12), tumor necrosis factor alpha (TNF alpha), interleukin-4 (IL-4), and interferon-gamma (INF-gamma) in T lymphocytes. Diabetic nephropathy and chronic glomerulonephritis were the most frequent primary pathologies in both groups of patients. The patients on CAPD without peritonitis expressed high levels of CD69 and the pro-inflammatory cytokines IL-1, IL-6, IL-12, TNF alpha, and IL-4, indicating in vivo immune activation similar to the group with peritonitis. In the group without peritonitis, 95% of samples displayed immunodeviation TH2. Just 5% of samples approached TH0, producing IFN-gamma. After mitogen activation, 45% of the samples stayed in TH2; 55% approached TH0. Patients with peritonitis produced high levels of IL-4 and little IFN-gamma, which indicates immunodeviation TH2 in 75% of samples; 25% approached TH0. When cells were stimulated by ionomicin and phorbol 12-myristate 13-acetate (PMA), more IFN-gamma appeared and high levels of IL-4 persisted in 75% of the samples, which looked like intent to correct the TH2 immunodeviation toward TH0. Patients on CAPD with and without peritonitis showed immune activation per se and high production of pro-inflammatory cytokines accompanied by a strong pattern of cytokine TH2 and a deficiency of IFN-gamma production, suggesting heavy immunodeviation TH2 and immunodeficiency TH1 (owing to the deficit of IFN-gamma). Finally, with in vitro immune stimulation, the TH2 pattern tried to approach TH0.

CD4-CD8 Ratio↗
PubMed2002

Peritonitis in continuous ambulatory peritoneal dialysis: cytokines in peritoneal fluid and blood.

Cytokines are soluble mediators of the immune system that regulate the response to antigens and microorganisms. In patients on continuous ambulatory peritoneal dialysis (CAPD) who have peritonitis, an inflammatory process exists that must be understood if susceptibility to, and the mechanisms of, complications such as fibrosis and others are to be understood. To that end, we studied 9 CAPD patients with peritonitis. The case series was conducted in Popayán, Colombia, at the RTS Cauca dialysis unit and the University of Cauca hospital, a tertiary health care facility. Peritonitis was diagnosed by standard clinical and laboratory criteria. Using flow cytometry, we measured the percentage production of intracellular cytokines [interleukin-1 alpha (IL-1 alpha), IL-6, IL-12, tumor necrosis factor alpha (TNF alpha), IL-4, and interferon-gamma (IFN-gamma) in T lymphocytes from blood and peritoneal fluid. Among the studied patients, all (100%) produced high levels of IL-1, IL-6, TNF alpha, IL-12, and IL-4 in both fluids (blood: 89% +/- 63% of cells; peritoneal fluid: 81.6% +/- 10.1% of cells). In blood, 25% of patients produced IFN-gamma (mean: 15.7% of cells), showing that 75% of patients had the TH2 pattern, and 25% were close to TH0. In peritoneal fluid, 34% of patients produced IFN-gamma spontaneously (mean: 24.5% of cells), indicating that 66% of patients were TH2, and 34% were close to TH0. After stimulation, expression of cytokines, including IFN-gamma (39% of T cells), was increased, and high production of IL-4 indicated that 25% of patients were TH2, and 75% were TH0. In peritoneal fluid, production of cytokines, including IFN-gamma, was increased, with high production of IL-4, indicating switching from TH2 (34% of patients) to TH0 (66% of patients). Of the studied patients, 35% had a CD4:CD8 ratio < 1.1 in blood, and also produced IL-12 (94.5% of cells) and IFN-gamma (30% of cells), as compared with patients in whom the CD4:CD8 ratio was > 1.2. Patients on CAPD who have peritonitis produce large amounts of pro-inflammatory and TH2 cytokines. More IFN-gamma is produced in peritoneal fluid than in blood, which suggests more inflammation. Immunodeviation TH2 is seen in blood and peritoneal fluid of CAPD patients with peritonitis. Patients with a CD4:CD8 ratio < 1.1 produce more IFN-gamma and IL-12, and are more able to switch from TH2 to TH0.

Antigens, CD↗