Biomedical subjects

T Tschernig

Publications and source records attributed to T Tschernig.

At least 19 recordsLinked to original sources

PubMed2006

Density of dendritic cells in the human tracheal mucosa is age dependent and site specific.

BACKGROUND: The mucosal immune system undergoes extensive changes in early childhood in response to environmental stimuli. Dendritic cells (DC) play a major role in the development of the immune system. However, few data exist on the influence of continuous environmental stimulation on the distribution and phenotype of human airway DC. METHODS: Human tissue samples are mostly paraffin embedded which limits the use of several antibodies, and respiratory tissue for cryopreservation is difficult to obtain. Human frozen post mortem tracheal tissue was therefore used for this study. Only samples with epithelial adherence to the basement membrane were included (n = 34). Immunohistochemical staining and sequential overlay immunofluorescence were performed with DC-SIGN and a panel of leucocyte markers co-expressed by DC. RESULTS: DC detected in the human tracheal mucosa using DC-SIGN correlated with the expression of HLA-DR, co-stimulatory and adhesion molecules. Higher cell densities were found at the ventral tracheal site of patients older than 1 year than in infants in the first year of life. CONCLUSION: The increasing population of mucosal DC with age could reflect immunological maturation.

Adult↗

PubMed2006

Non-steroidal and steroidal anti-inflammatory drugs vary in their modulation of dendritic cell function in the elicitation phase of allergic contact dermatitis.

The role of dendritic cells (DCs) in allergic contact dermatitis has been clearly demonstrated for the induction phase. However, the situation during the elicitation phase is very complex within a distinct inflammatory response. This study was performed to exploit DC migration in the elicitation phase in a mouse model of allergic contact dermatitis and to evaluate the effects of steroidal and non-steroidal anti-inflammatory drugs (NSAIDs) on DC migration through skin in the elicitation phase of allergic contact dermatitis. Topically and systemically administered acetylsalicylic acid (ASA) did not reduce the inflammatory response. However, systemically administered ASA significantly reduced the DC migration to the draining lymph node. In contrast, topically administered indomethacin reduced the inflammatory response, but had only minor effects on DC migration, whereas diflorasone diacetate reduced both inflammatory reaction and DC migration. Thus, NSAIDs may differ in their inhibitory action in immunological inflammation.

Animals↗

PubMed2006

Coincidence of different structures of mucosa-associated lymphoid tissue (MALT) in the respiratory tract of children: no indications for enhanced mucosal immunostimulation in sudden infant death syndrome (SIDS).

Mucosa-associated lymphoid tissue (MALT) is the principal inductive site for mucosal immune responses that are capable of T and B cell responses and antigen-specific responses. In previous independent studies different structures of MALT, e.g. bronchus-, larynx- and nose-associated lymphoid tissue (BALT, LALT, NALT) have been described separately in various frequencies in the human respiratory tract over life spans. Because upper respiratory tract infections are common in infants, dysregulations of mucosal immune responses might be seriously involved in the aetiology of sudden infant death syndrome (SIDS). In the present study the coincidental occurrence of the three different MALT structures in the respiratory tract within the same patients were studied, and cases of SIDS and children who had died from different traumatic and natural causes of death (non-SIDS) were compared. First, the frequency of BALT and LALT in 46 children (35 SIDS, 11 non-SIDS) with or without NALT were examined. A tendency was found of a coincidence of respiratory MALT structures. In 50 additional cases of infant death (30 SIDS, 20 non-SIDS) from the multi-centric German Study on Sudden Infant Death Syndrome (GeSID) where death had occurred in the first year of life, the coincidence was evaluated. A coincidental occurrence of BALT, LALT and NALT or BALT and LALT (each about 30%) was found in both groups, whereby the coincidence in SIDS and the control patients did not differ. Interestingly, the children with coincidental MALT were strikingly older, supporting the hypothesis of respiratory MALT formation via environmental stimulation over time.

Bronchi↗

PubMed2005

Mini-laparotomy and full laparotomy, but not laparoscopy, alter hepatic macrophage populations in a rat model.

BACKGROUND: Immune function is better preserved by laparoscopic versus conventional surgery. Numerous mediators of the systemic trauma response are synthesized and/or regulated by the liver. However, it has been stated that the advantages of laparoscopic surgery are no more obvious when conventional operations are performed via mini-laparotomy. We set out to compare the impact of laparoscopy and mini- and full laparotomy on the hepatic macrophage populations. METHODS: Male Lewis rats were subjected to anesthesia alone (control), mini-laparotomy (1 cm), full laparotomy (7 cm), or laparoscopy for 60 min. Endpoints were the total protein in the peritoneal lavage fluid, hepatic ED-1 cells (recruited monocytes), hepatic ED-2 cells (Kupffer cells), the expression of OX-6 in the liver, and C-reactive protein (CRP) in plasma. RESULTS: Protein in the peritoneal lavage fluid increased significantly after all interventions. Full laparotomy was accompanied by an enhancement in ED-1-positive monocytes in the liver parenchyma compared to all other groups (p < 0.001). Mini- and full laparotomy led to an increase in ED-2-positive Kupffer cells (p < 0.001). Laparoscopy did not affect the number of monocytes/macrophages. There was no significant alteration of OX-6 expression in either group. No change in the cellular composition in the periportal fields was observed. The CRP plasma levels did not significantly differ between groups. CONCLUSIONS: Laparoscopy completely prevents hepatic macrophage populations from expansion and normal cell disposition is preserved. Laparotomy, irrespective of incision size, increases the number of Kupffer cells. Moreover, full laparotomy, but not mini-laparotomy or laparoscopy, causes an increase in hepatic monocyte recruitment. The regulating pathways after surgery differ from other immunologic challenges, such as sepsis, in which immunocompetent cells accumulate and are stimulated in the periportal fields.

Animals↗

PubMed2005

Cilomilast, tacrolimus and rapamycin modulate dendritic cell function in the elicitation phase of allergic contact dermatitis.

BACKGROUND: Cilomilast and tacrolimus as well as rapamycin are potential drugs for the treatment of allergic skin diseases like atopic dermatitis and allergic contact dermatitis. OBJECTIVES: To compare the in vitro and in vivo immunomodulatory effects of the phosphodiesterase 4 inhibitor cilomilast with those of tacrolimus and rapamycin. METHODS: The in vitro action of cilomilast, tacrolimus and rapamycin were tested in a mixed leucocyte reaction (MLR). In vivo, the inhibitory action of the immunomodulatory drugs was compared in the toluene-2,4-diisocyanate (TDI)-induced allergic inflammatory response with particular focus on dendritic cell (DC) function. RESULTS: Cilomilast, tacrolimus and rapamycin were all able to inhibit DC-mediated T-cell activation in a MLR. But it was demonstrated for cilomilast that the target cells are T cells rather than DC. In vivo, a combination of systemic and topical administration of each of these three substances significantly inhibited swelling in the murine ear 16 h after TDI challenge. There was also a reduction in the weight of the draining auricular lymph node, in lymphocyte cell count, and in the number of emigrated DC. The density of Langerhans cells in the epidermis was correspondingly higher in mice treated with cilomilast, tacrolimus and rapamycin than in those treated with vehicle. All three substances were found to inhibit DC migration ex vivo in a skin DC migration assay performed on ear tissue after TDI challenge. CONCLUSIONS: DC migration into the draining lymph node also takes place in the elicitation phase of allergic contact dermatitis and this migration can be influenced by tacrolimus and rapamycin, and, to a lesser extent, by cilomilast.

Animals↗

PubMed2005

CD26 (dipeptidyl-peptidase IV)-dependent recruitment of T cells in a rat asthma model.

CD26 truncates several chemokines as well as neuropeptides and influences immune responses via modulation of cell adhesion and T cell activation, suggesting an involvement of CD26 in asthmatic and airway inflammation. Therefore, Fischer 344 (F344), Brown Norway (BN) and Lewis (LEW) rat strains, which differ in their CD26-like enzymatic activity, were compared using an asthma model. Additionally, two CD26-deficient mutant F344 rat substrains were included and compared to the wild-type F344 substrain. Immunization was performed twice with ovalbumin (OVA), and 2 weeks later the rats were challenged with OVA intratracheally Flow cytometry (FACS) analysis of different leucocyte subsets as well as enzyme-linked immunosorbent assay (ELISA) for IgE levels in the blood and bronchoalveolar lavage (BAL) were performed 24 h after challenge. LEW rats with the lowest CD26 activity among the rat strains investigated here displayed significantly reduced CD4+ T cell numbers in the BAL compared to wild-type F344 and BN rats. Moreover, in asthma, the ratio of CD26+ to CD26- T cell receptor (TCR)-positive cells increased significantly in F344 and LEW but not BN rats. Most intriguingly, in both CD26-deficient F344 rat substrains the number of CD4+ T lymphocytes was markedly reduced compared to wild-type F344. The decrease in T cell recruitment observed in the CD26-deficient rats was associated with significantly reduced OVA-specific IgE-titres. This is the first report to show a remarkably reduced T cell recruitment in rat strains that either lack or exhibit reduced CD26-like enzymatic activity, suggesting a role for CD26 in the pathogenesis of asthma via T cell-dependent processes such as antibody production.

Animals↗

PubMed2004

A comparison of two types of free bone grafts as transport discs in segmental distraction for reconstruction of calvarial bone defects: an experimental study.

INTRODUCTION: Several investigations over the past few years have shown that the importance of preserving the blood supply of the transport disc during segmental distraction has been overestimated. It was clearly demonstrated that distraction osteogenesis by local bone transportation could be achieved even with free bone grafts. So far, there have been no systematic investigations into how different types of free bone grafts vary in their function and suitability as transport discs in segmental craniofacial distraction. The aim of this study was to develop criteria to aid the clinician in selecting the most suitable free bone graft for distraction purposes. MATERIALS AND METHODS: Under general anesthesia, calvarial defects measuring 6 x 5 cm were created in 12 adult black head sheep in order to reconstruct them by segmental distraction using two different types of bone grafts as transport discs. Group 1 (n=6) received autotopical membranous bone of the calvarium as the transport segment, while group 2 (n=6) received heterotopical enchondral material from the iliac crest. Distraction was started postoperatively after 5 days at 0.6 mm/day and continued for 7 weeks. After a further 6 weeks of consolidation, the animals were killed and specimens examined macroscopically, radiographically and histologically. RESULTS: The significantly better quality of bone regenerates of group 1 was clearly influenced by the significantly better stability of the transport disc's connection to the distraction device, the calvaria grafts showing better volume stability and better mechanical resistance during transport than the iliac bone. The influence of both types of bone grafts on the macro- and microstructure of the newly formed bone was clearly evident. The mineralization density of group 2 regenerates was significantly lower than that of group 1 specimens. CONCLUSION: High mechanical stability of the bone graft is a very important point to consider when selecting a free graft for use as transport disc in local bone transport, especially if transport is necessary over long distances.

Animals↗

PubMed2004

Presence of dendritic cells, T lymphocytes, macrophages, B lymphocytes and glandular tissue in the human fetal larynx.

OBJECTIVE: The laryngeal mucosa starts to be exposed to infectious agents immediately after birth. The course of laryngeal infections in young children differs significantly from that in adults. The first line of defense encountered by an inhaled infectious agent is the mucosa-associated immune system, which includes immunocompetent cells and secretory components. The cellular elements are partially organized in a typical morphological pattern known as mucosa-associated lymphoid tissue (MALT). Differences in the ability of young children and adults to react to a laryngeal infection raise the questions of whether and to what extent immunocompetent cells are already present in the larynx at birth. These questions were investigated in this study. MATERIAL AND METHODS: Dendritic cells, T lymphocytes, B lymphocytes, macrophages and glands were examined and detected in an (immuno-)histological study of 8 fetal larynges (14th-22nd week of gestation). RESULTS: Immunocompetent cells and glands were present mainly in the epi- and subglottic regions and ventricular folds, whereas the glottis was largely spared. The pattern of distribution was scattered and no organized MALT was seen. CONCLUSION: Essential cell populations of a mucosa-associated immune system for the initiation of an immune response may exist in the human larynx at birth.

Antibodies, Monoclonal↗

PubMed2004

TARC and RANTES, but not CTACK, are induced in two models of allergic contact dermatitis. Effects of cilomilast and diflorasone diacetate on T-cell-attracting chemokines.

BACKGROUND: Skin-infiltrating T cells play a predominant role in allergic and inflammatory skin diseases such as atopic dermatitis and allergic contact dermatitis. These T cells are attracted by chemotactic factors, e.g. RANTES (regulation on activation, normal T cell expressed and secreted; CCL5), TARC (thymus and activation regulated chemokine; CCL17) and CTACK (cutaneous T-cell attracting chemokine; CCL27). OBJECTIVES: To investigate which T-cell-attracting chemokines are involved in allergic contact dermatitis in mice. METHODS: Allergic contact dermatitis was induced by application of dinitrochlorobenzene (DNCB) or toluene-2,4-diisocyanate (TDI), and chemokine concentrations were determined by enzyme-linked immunosorbent assay. The effects on chemokine concentrations of the highly selective phosphodiesterase 4 inhibitor cilomilast and the glucocorticoid diflorasone diacetate were studied in mouse ears. RESULTS: RANTES and TARC were elevated in both models of allergic contact dermatitis 24 h after challenge, whereas CTACK remained unchanged. The increase in RANTES was diminished in mouse ears pretreated with cilomilast or diflorasone diacetate. TARC was reduced by diflorasone diacetate in the DNCB model but was highly induced in the TDI model; in contrast, TARC was not influenced by cilomilast. CONCLUSIONS: TARC and RANTES, but not CTACK, are involved in these two models of allergic contact dermatitis.

Animals↗

PubMed2003

Effect of anti-nerve growth factor on early and late airway responses in allergic rats.

BACKGROUND: The increased production of nerve growth factor (NGF) has been associated with allergen-induced airway hyperresponsiveness and enhanced airway inflammation in experimental models of asthma. The aim of this study was to investigate whether a local application of anti-NGF to the lungs may affect the allergen-specific early (EAR) and late (LAR) airway responses to ovalbumin (Ova) of Ova-sensitized brown Norway rats. METHODS: Rats were sensitized systemically with Ova and were boosted twice intratracheally with Ova aerosol using a microsprayer. Two hours before every boost, the animals were pretreated either with aerosolized anti-NGF or with a control antibody. On day 21, all animals were challenged with inhalational Ova aerosol and pulmonary resistance was recorded in anesthetized, orotracheally intubated animals during the early and late asthmatic responses. In addition, differential cell counts from bronchoalveolar lavage and serum immunoglobulin E (IgE) levels were determined 48 h post-Ova challenge. RESULTS: Pretreatment with anti-NGF significantly attenuated the EAR but had no significant effect on the LAR. Serum IgE levels and inflammatory cell influx into the lungs were not affected by anti-NGF pretreatment. CONCLUSION: The data from this study suggest that NGF is directly involved in the development of the EAR without affecting the inflammatory airway response or LAR.

Aerosols↗

PubMed2003

Nasal-associated lymphoid tissue (NALT): frequency and localization in young children.

In mucosal immunology nasal-associated lymphoid tissue (NALT) is taken as a constitutive structure of the nasal immune system and as a target tissue in strategies of local defence and an induction site for vaccination. These concepts are based on findings in rodents, but it has not been investigated systematically whether NALT also is present in humans and if so in which amount and localization. In a postmortem study the presence of NALT in humans is documented as a morphologically distinct structure additional to the lymphoid structures of the Waldeyer's ring. Human nasal tissue blocks of 150 children who had died in the first two years of life either of sudden infant death (n = 109) without signs of respiratory tract infections or of different traumatic (n = 22) and natural causes of death (n = 19) were obtained using a specific autopsy-technique and were investigated systematically using histology. Clearly in contrast to rodents human NALT was found disseminated in the nasal mucosa with typical morphological features in 38% of all children, mainly in the middle concha, with similar morphology and frequency in the examined groups. No correlation was found between the presence of NALT and the cause of death and especially the grade of inflammation in general. Therefore, NALT might be the morphological basis for inhalative vaccination strategies in young children and play a role in mucosal host defence.

Animals↗

PubMed2003

Alveolar macrophages are the main source for tumour necrosis factor-alpha in patients with sarcoidosis.

Tumour necrosis factor (TNF)-alpha is known to play a major role in the formation of noncaseating granuloma, a hallmark of sarcoidosis. The main cellular source in situ is still ambiguous. Serial sections of transbronchial biopsies from 14 patients with and 12 without sarcoidosis were studied, using immunohistochemistry (IHC), for TNF-alpha, T-cells (CD3), macrophages (CD68), and epithelial cells (MNF116). TNF-alpha spontaneously released (sr-TNF-alpha) by freshly isolated bronchoalveolar lavage cells, isolated from the same patients and cultured without any stimulus over a 24-h period was measured using an enzyme-linked immunosorbent assay. IHC revealed colocalisation of TNF-alpha with CD68 cells only. Cases with TNF-alpha tissue immunoreactivity exhibited higher sr-TNF-alpha (1,667 +/- 504 pg x mL(-1)) than cases without tissue immunoreactivity (211 +/- 60 pg x mL(-1)). In an explorative approach, a subgroup of patients could be identified and characterised by the presence of alveolar macrophage aggregates. It was found that sr-TNF-alpha was highest in this subgroup (2,700 +/- 769 pg x mL(-1)) compared with patients with normal histology (221 +/- 61 pg x mL(-1)) or with prominent granuloma (460 +/- 137 pg x mL(-1)), whereas in most clinical parameters this subgroup was intermediate. The findings from this study strongly corroborate the view that alveolar macrophages are the main cellular source for tumour necrosis factor-alpha in the initial phase of sarcoidosis. The authors suggest that in these patients, aggregates of alveolar macrophages may represent at least predecessors to granulomas if not granulomas in statu nascendi.

Adult↗

PubMed2002

Increase of inactive intra-alveolar surfactant subtypes in lungs of asthmatic Brown Norway rats.

We tested the hypothesis whether allergic airway inflammation in ovalbumin sensitized and challenged Brown Norway rats is associated with intrinsic surfactant alteration and dysfunction. The determination of intra-alveolar surfactant subtypes and alveolar edema within their original microenvironment is only possible using an ultrastructural stereological approach. Therefore both lungs of control and asthmatic rats were fixed by vascular perfusion. The volume fractions of surfactant subtypes and the epithelial surface fraction covered with alveolar edema were determined by point and intersection counting. Furthermore, lung resistance was measured by means of whole-body plethysmography. The surface activity of surfactant from bronchoalveolar lavage was determined as minimum surface tension at minimal bubble size with a pulsating bubble surfactometer. Compared with controls, in asthmatics (1) the fraction of inactive unilamellar forms was significantly increased from 56% to 66%, (2) the fraction of alveolar epithelium covered with alveolar edema visible by light microscopy was significantly increased from 0.7% to 5.0%, (3) the fraction of alveolar epithelium covered with fluid seen by electron microscopy expanded significantly from 5% to 21%, (4) lung resistance was significantly elevated from 14% to 86% and (5) surface tension was enhanced from 6 mN/m to 12 mN/m. Thus, the inflammatory process after allergen challenge of sensitized Brown Norway rats causes intra-alveolar surfactant alterations. These surfactant alterations might contribute to small airway dysfunction.

Administration, Inhalation↗

PubMed2002

Pulmonary microbial infection in mice: comparison of different application methods and correlation of bacterial numbers and histopathology.

Many investigations have been performed in characterising experimental bacterial infections in the lung of mice using several pathogens. Robust experimental pulmonary infection models require a reproducible method of application with defined numbers of pathogens to the respiratory tract without contaminating extrapulmonary tissues. At the same time trauma due to the experimental procedure should be kept to a minimum. So far several routes of administration have been used but a systematic comparison of these methods is still missing. Here we provide a comprehensive evaluation of view controlled i.t. instillation, tracheotomy, intranasal application, blind instillation and aerosol infection. An infection dose of up to 5 x 10(4) bacteria (L. monocytogenes) was applied to a group of ten mice by each technique and the animals were killed after 1 h or 24h. The number of viable bacteria was estimated by plating homogenates of the lungs and spleens. In addition, pathological effects on lung tissue were examined by histology 24h after infection. The highest reproducibility was achieved after applying Listeria directly in the trachea under view or by tracheotomy. However, mice were severely affected in their vitality after tracheotomy. Thus, for topical application of bacterial suspension into the lung the view controlled i.t. instillation is most appropriate.

Animals↗

PubMed2002

Adenoviral gene transfer in a rat fracture model.

For the enhancement of fracture healing, either purified proteins or vectors for expression of growth factors in situ may be used. Adenoviral vectors directly convert cells to express a transgene. However, the cell types which are preferentially infected and the time of expression during fracture healing are currently not known. The adenoviral type 5 vectors used in this study are replication incompetent viruses, one encoding beta-galactosidase (beta-GAL) and one green fluorescent protein. Femora of 35 Sprague-Dawley rats were fractured. Three days after stabilization with Kirschner wire, 10(12) pfu viral suspension were injected into the fracture zone. As a control, five animals received injections of adenovirus type 2. Animals were sacrificed after 3 days, 1, 2 and 4 weeks. Fractures healed radiographically within 2-3 weeks. All specimens were examined for beta-GAL and green fluorescent protein (GFP) expression. Fibroblast and osteoblasts within callus tissue displayed a high transgene expression (week 1). A decrease of expression was observed during the observation period. In this experimental study, we have demonstrated that all cells of the primary callus can be transfected using adenoviral vectors, which provide a tool to further investigate adenoviral transfer of growth factors such as bone morphogenetic protein-2 (BMP-2).

Adenoviridae↗

PubMed2001

Complement factors C3a and C5a are increased in bronchoalveolar lavage fluid after segmental allergen provocation in subjects with asthma.

Allergic asthma is thought to be the result of an inappropriate specific immune response against common environmental antigens. However, studies of animal asthma models have also linked the innate immune system, in particular complement factors C3a and C5, to murine airway hyperresponsiveness. Because the possible role of these anaphylatoxins in patients with asthma is not understood, we tested the hypothesis that C3a and C5a will increase in the bronchoalveolar lavage (BAL) fluid of patients with asthma after segmental allergen provocation. In a group of 15 subjects with mild asthma we found a significant upregulation of C3a and C5a 24 h after allergen challenge compared with baseline values (p < 0.01). In a control group of healthy volunteers the concentrations remained basically unchanged. Furthermore, we found a strong correlation between both anaphylatoxins and the number of eosinophils (p < 0.01) and, to a lesser degree, with the number of neutrophils (p < 0.05) in BAL fluid. These data suggest a contribution of anaphylatoxins C3a and C5a to the pathogenesis in asthma. However, the pathogenic role of these substances in relation to asthma remains to be elucidated, for example, by using anaphylatoxin receptor blockers as a possible new therapeutic principle.

Adult↗

PubMed2001

Lymphocytes in the bronchoalveolar space reenter the lung tissue by means of the alveolar epithelium, migrate to regional lymph nodes, and subsequently rejoin the systemic immune system.

Lymphocytes in the bronchoalveolar space are routinely obtained and examined in lung diseases such as asthma or sarcoidosis. In a pig model, labeled lymphocytes were found in regional lymph nodes after intrabronchial instillation, indicating that reentry of lymphocytes from the bronchoalveolar space into the body is possible. In the present study, the route and kinetics of the reentry of bronchoalveolar lymphocytes were investigated in a congenic rat model using immunohistochemistry on cryostat and semithin sections and confocal laser scanning microscopy. As early as 15 min after intratracheal instillation lymphocytes were found to leave the bronchoalveolar space by transmigration through alveolar but not bronchial epithelium and were observed in interstitial alveolar tissue. At 6 hr after intratracheal instillation, T and B lymphocytes appeared in the draining lymph nodes of the lung with an increase after 24 and 48 hr. The kinetic pattern clearly differed in nondraining lymph nodes and other organs. After 6 hr, only single cells were found in nondraining lymph nodes, spleen, and blood with a slight increase after 24 hr, and only occasionally were single cells seen in the liver, thymus, or Peyer's patches 24 and 48 hr after instillation. In conclusion, T and B lymphocytes can leave the alveolar space by reentry into the lung tissue through alveolar epithelium. They reach regional lymph nodes by means of lymphatic vessels and are then distributed all over the body to rejoin the systemic immune system. Coming into contact with environmental antigens, these lymphocytes could perform an important function in the lung immune system and might be a target for inhalative therapy.

Animals↗

PubMed2001

Evidence of recurrent atypical meningioma with rhabdoid transformation and expression of pyrogenic cytokines in a child presenting with a marked acute-phase response: case report and review of the literature.

Children presenting with acute systemic illnesses that lack specific clinical or serological defining features may be diagnosed as having a chronic infection, an atypical systemic vasculitis or a connective tissue disease, but often turn out to have occult neoplasias. Cytokines have been implicated in causing many of the systemic effects in such cases. In this study, we describe the case of a 9-year-old boy presenting at an interval of 18 months with a marked acute-phase response due to a recurrent atypical meningioma with rhabdoid transformation of the tentorium cerebelli. Resection of the recurrent tumor was curative. We evaluated in detail the local and systemic production of cytokines released by the primary and the recurrent tumor. Blood and CSF samples were taken pre-, intra-, and postoperatively, and the production of IL-6, IL-1beta, and TNF-alpha was measured by enzyme-linked immunosorbent assays (ELISA). The level of IL-6 in CSF was about 150-fold increased before tumor resection, normalizing postoperatively. On the contrary, the levels of IL-1beta and TNF-alpha in CSF and of IL-6, IL-1beta, and TNF-alpha in serum were pre-, intra-, and postoperatively within normal limits. Cytokine production was also evaluated immunohistochemically, and confirmed strong IL-6 and TNF-alpha expression in the primary and the recurrent tumor, while expression of IL-1beta was lacking. The scattered MHC class II- and leukocyte common antigen (LCA)-expressing inflammatory cells, which were infiltrating exclusively the tumoral stroma, had no detectable cytokine immunoreactivity. We conclude that chronic IL-6 and TNF-alpha production by the tumor cells in this patient was responsible for the severe systemic illness with which he presented.

Acute Disease↗