Aspergillus fumigatus in cystic fibrosis: An update on immune interactions and molecular diagnostics in allergic bronchopulmonary aspergillosis.

A wide spectrum of pathological conditions may result from the interaction of Aspergillus fumigatus and the immune system of its human host. Allergic bronchopulmonary aspergillosis is one of the most severe A. fumigatus-related diseases due to possible evolution toward pleuropulmonary fibrosis and respiratory failure. Allergic bronchopulmonary aspergillosis occurs almost exclusively in cystic fibrosis or asthmatic patients. An estimated 8%-10% of patients with cystic fibrosis experience this condition. The diagnosis of allergic bronchopulmonary aspergillosis relies on criteria first established in 1977. Progress in the understanding of host-pathogen interactions in A. fumigatus and patients with cystic fibrosis and the ongoing validation of novel laboratory tools concur to update and improve the diagnosis of allergic bronchopulmonary aspergillosis.

Aspergillus fumigatus components distinguish IgE but not IgG4 profiles between fungal sensitization and allergic broncho-pulmonary aspergillosis.

Aspergillus fumigatus is the causative agent of allergic broncho-pulmonary aspergillosis. Prompt and accurate diagnosis may be difficult to achieve with current clinical and laboratory scores, which do not include immune responses to recombinant A. fumigatus allergens. We measured specific immunoglobulin E and G4 directed to recombinant A. fumigatus allergens in 55 cystic fibrosis patients without allergic broncho-pulmonary aspergillosis but sensitized to A. fumigatus and in nine patients with allergic broncho-pulmonary aspergillosis (two with cystic fibrosis and seven with asthma). IgG4 responses to recombinant A. fumigatus allergens were detected in all patients, but neither prevalence nor levels were different between the two patient groups. On the other hand, both prevalence and levels of IgE responses to Asp f 3, Asp f 4, and Asp f 6 helped distinguish allergic broncho-pulmonary aspergillosis from A. fumigatus sensitization with good negative and positive predictive values.

[Use of MRI before biopsy in diagnosis of prostate cancer: Single-operator study]. / Utilité de l'IRM pré-biopsique dans la détection du cancer de prostate: étude mono-opérateur.

UNLABELLED: The diagnostic for prostate cancer is changing. To improve the detection of this cancer, urologists expect a lot from the contribution of magnetic resonance imaging (MRI). What is the role of this imaging in prostate cancer detection? This is a retrospective study, from 2011 to 2013, mono-centric and single-operator. Of the 464 needle biopsy of the prostate (BP), we excluded those with PSA>20 ng/mL or digital rectal examination (DRE)>T3. The remaining 430 BP were submitted or not to a 1.5 tesla MRI with pelvic antenna. The primary aim is the overall detection of prostate cancer. Secondary aim was the detection rate during the first series of BP and repeat BP, between the two groups in the MRI group. MRI and MRI without populations are comparable for age (63.3 vs 64.6), PSA (6.10 vs 6.13), DRE>T1c, prostate volume (55.4 cm(3) vs 51.7 cm(3)). There is no significant difference in overall detection between the two groups (P=0.12). There is no significant difference in cancer detection between the first BP (P=0.13) and the repeat BP (P=0.07). There is a significant difference in the early detection of BP MRI group (P=0.03) but not for the BP repeat MRI group (P=0.07). For 108 BP iterative MRI group, there were 67 BP targeted "mentally" with MRI: 18 cancers were detected, making a 25% detection rate. This study helps to highlight the value of MRI in the early rounds of BP but we can ask the value of this imaging during repeat biopsies. Targeted biopsies "mentally" do not have the expected detection sensitivity and seems to require a three-dimensional reconstruction to be more effective. LEVEL OF EVIDENCE: 5.

Reduced interleukin-12 release from stimulated monocytes in patients with sepsis after major cancer surgery.

BACKGROUND: Major cancer surgery is a high-risk situation for sepsis in the post-operative period. The aim of this study was to assess the relation between the monocyte production of IL-12 and the development of post-operative sepsis in patients undergoing major cancer surgery. METHODS: In 19 patients undergoing major cancer surgery, the production of cytokines by basal and lipolysaccharide (LPS)-stimulated monocytes was measured before and after (from day 1 to day 3 and day 7) surgery. Seven of them developed a post-operative sepsis. Ten healthy volunteers were used as controls for the assessment of pre-operative values. RESULTS: Before surgery, the production of interleukin (IL)-12 p40 by LPS-stimulated monocytes was similar in the patients and the healthy volunteers. The production of IL-12 p40 by unstimulated monocytes was higher in the patients than in the healthy volunteers. IL-12 production did not differ between the septic and the non-septic patients. After surgery, the production of IL-12 p40 was dramatically reduced in the LPS-stimulated monocytes of the septic patients from day 1 to day 3, as compared with that of the non-septic patients. Before surgery, the production of IL-6, IL-10, and IL-1 receptor antagonist (IL-1ra) in the patients was significantly higher than that of the healthy volunteers for both stimulated and unstimulated monocytes. After surgery, the production of these cytokines by both stimulated and unstimulated monocytes of the septic patients was similar to that of the non-septic patients. Intragroup analysis showed significant changes for IL-6, IL-10, and IL-1ra under all conditions, with the exception of changes in unstimulated monocytes of septic patients that were not significant for IL-10 release. CONCLUSION: After surgery, the septic patients showed drastic failure to up-regulate monocyte LPS-stimulated production of IL-12 p40.

The sexual dimorphism of anticardiolipin autoantibodies in acute Q fever patients.

OBJECTIVES: Q fever is a zoonotic disease caused by Coxiella burnetii which affects men more than women (sex ratio men/women: 2.2). Acute Q fever complications are associated with elevation of anticardiolipin (aCL) antibodies. Here, we investigate the sexual dimorphism of aCL antibodies during acute C. burnetii infection. METHODS: IgG aCL antibodies were evaluated at the time of Q fever serological diagnosis with enzyme-linked immunosorbent assay. Results were analysed according to sex. RESULTS: Among the 1323 patients with Q fever tested for aCL, 1013 had acute Q fever (692 men/321 women) and 310 had persistent focalized infection (226 men/84 women). In cases of acute Q fever, men presented a significantly higher proportion of positive aCL antibodies (351/692, 50.7%) than women (113/321, 35.2%) (p <0.05). In addition, men had significantly higher aCL antibodies levels than women (p <0.001). CONCLUSIONS: We highlight a relationship between sex and markers of autoimmunity during Q fever. Further investigations are necessary to better understand the mechanisms of this sexual dimorphism.

[Description and results of a prospective study on a new physiotherapy method in the management of postprostatectomy urinary incontinence]. / Description et résultat d'une étude prospective portant sur une nouvelle méthode de kinésithérapie dans la prise en charge de l'incontinence urinaire postprostatectomie.

OBJECTIVE: Prospective evaluation of the short-, medium- and long-term efficacy of the "ABDO-MG concept" technique in the rehabilitation of urinary incontinence following radical prostatectomy (abdominal or laparoscopic approach). METHODOLOGY: Fifty-three patients suffering from clinical urinary stress or triple incontinence (pure stress incontinence, incontinence due to bladder instability or sphincteric insufficiency) took part in the study. Rehabilitation treatment, begun six weeks before the operation, continued during the immediate postoperative period, at home and at the physiotherapist's office for three to 12 months until the urinary incontinence had disappeared or was considered to be minimal and acceptable, therefore tolerated. The exercises were performed according to a strict protocol defined by the inventor of the concept, involving expiration into a specific end-piece (called "sound end-piece") and connection with an abdominal neurostimulator for which the current is triggered and maintained by the sound of the patient's breathing into the sound end-piece. The efficacy of this concept was confirmed by a comparative trial before and during rehabilitation and then at the end of treatment. There was triple monitoring: evaluation by LFT noting, for each breath, the flowrate/volume curve and FEV1/s, clinical abdominal testing with monitoring of abdominal movement both vertically and horizontally during coughing and a "pad test" at home, assessing the quantity of nocturnal and diurnal urinary leakage relative to each patient's activity. RESULTS: The results were meaningful and significant. The improvement of the flowrate/volume curve and FEV1/s varied between 1.4436 and 1.1209 L. Abdominal testing showed constant positive evolution in the correction of abdominal incompetence under stress (test improved by one point on a negative graduation of -1 to -3). The home "pad test" confirmed a highly significant result with leakage virtually disappearing, sometimes falling from nearly 800 cc to just a few drops at the end of treatment. The subjective results were marked by the improvement in various dysfunctions within the context of abdominal incompetence increased by the abdominal surgery. CONCLUSION: This prospective study was the first to provide an evaluation of the abdominal motor score and the relationship between expiration thrust and pelviperitoneal protection.

Sex and bacterial infectious diseases.

Most infectious diseases are unequally distributed between male and female subjects. This sex dimorphism is confirmed by epidemiologic studies which suggest an increased number of male septic patients, while, due to the class age of septic patients, an overrepresentation of female patients would be expected. Lifestyle, recreational activities, professional exposition and access to care are plausible reasons for this dimorphism. However, biological differences should be carefully considered, particularly the weight of X-linked variability and the role of sex hormones. Animal models clearly show that clinical response to infection is more exuberant in males than in females. This is partly explained by an attenuation of the inflammatory response by female sex hormones. However, the translation from experimental studies to the bedside remains challenging as a result of confounding factors like age, hormone changes and response to treatment.

Higher education at the Institut Hospitalo-Universitaire Méditerranée Infection.

Since its creation in 2011, the Institut Hospitalo-Universitaire Méditerranée Infection (IHU MI) has devoted a major part of its funding to support higher education programs. In 2017, on a recurrent budget of 5.8 million Euros per year, 2.9 (50%) were spent on infrastructure, mostly for maintenance and equipment of our new building. Among the remaining 2.9 million Euros, 2.3 (80%) have been dedicated to support higher education programs.

Cytomegalovirus reactivation enhances the virulence of Staphylococcus aureus pneumonia in a mouse model.

OBJECTIVES: Cytomegalovirus (CMV) reactivation in intensive care unit patients may increase mortality and favour bacterial pneumonia. We developed a murine model to compare the severity of staphylococcal pneumonia after CMV reactivation and in CMV-negative mice. METHODS: Balb/c mice were primo-infected with murine cytomegalovirus (MCMV n=90) or received saline (control n=90). After latency, all mice underwent caecal ligation and puncture to trigger MCMV reactivation in MCMV primary-infected mice. Surviving animals received an intra-nasal inoculation with methicillin-susceptible Staphylococcus aureus (MSSA) to induce pneumonia. Mortality, lung bacterial count, histology and interferon-alpha and gamma serum levels were compared in MCMV reactivated and control mice 2, 5 and 15 days after pneumonia. RESULTS: After MSSA pneumonia, MCMV mice showed a trend towards a higher mortality (9.4% versus 0%; p 0.09) and a higher weight loss (2.2 (0.6-4.1 g) versus 0.7 (-0.3 to 1.3 g); p 0.005). The lung bacterial count was higher in MCMV mice 2 days (5×103 (103 to 3×105) versus 102 (0 to 4×102) CFU/lung; p 0.007) and 5 days (2.5×104 (1.6×104 to 6.5×105) versus 15 (10-40) CFU/lung; p 0.005) after MSSA pneumonia. 8/40 (20%) MCMV mice developed lung abscesses compared to 0% in control (p 0.011). Interferon-alpha serum levels 2 days after staphylococcal pneumonia were higher in MCMV mice. CONCLUSIONS: MCMV reactivation decreased lung bacterial clearance and favoured the development of staphylococcal abscessing pneumonia. CMV reactivation may be responsible for a higher susceptibility to bacterial sepsis.

Intact interferon-γ response against Coxiella burnetii by peripheral blood mononuclear cells in chronic Q fever.

OBJECTIVES: Q fever is caused by Coxiella burnetii, an intracellular bacterium that infects phagocytes. The aim of the present study was to investigate whether the C. burnetii-induced IFN-γ response is defective in chronic Q fever patients. METHODS: IFN-γ was measured in supernatants of C. burnetii-stimulated peripheral blood mononuclear cells (PBMCs) of 17 chronic Q fever patients and 17 healthy individuals. To assess IFN-γ responses, expression profiles of IFN-γ-induced genes in C. burnetii-stimulated PBMCs were studied in six patients and four healthy individuals. Neopterin was measured in PBMC supernatants (of eight patients and four healthy individuals) and in sera (of 21 patients and 11 healthy individuals). In a genetic association study, polymorphisms in genes involved in the Th1-cytokine response were analysed in a cohort of 139 chronic Q fever patients and a cohort of 220 control individuals with previous exposition to C. burnetii. RESULTS: IFN-γ production by C. burnetii-stimulated PBMCs from chronic Q fever patients was significantly higher than in healthy controls. Many IFN-γ response genes were strongly upregulated in PBMCs of patients. Neopterin levels were significantly higher in PBMC supernatants and sera of patients. The IL12B polymorphisms rs3212227 and rs2853694 were associated with chronic Q fever. CONCLUSIONS: IFN-γ production, as well as the response to IFN-γ, is intact in chronic Q fever patients, and even higher than in healthy individuals. Polymorphisms in the IL-12p40 gene are associated with chronic Q fever. Thus, a deficiency in IFN-γ responses does not explain the failure to clear the infection. The genetic data suggest, however, that the IL-12/IFN-γ pathway does play a role.

Involvement of matrix metalloproteinases in chronic Q fever.

OBJECTIVES: Chronic Q fever is a persistent infection with the intracellular Gram-negative bacterium Coxiella burnetii, which can lead to complications of infected aneurysms. Matrix metalloproteinases (MMPs) cleave extracellular matrix and are involved in infections as well as aneurysms. We aimed to study the role of MMPs in the pathogenesis of chronic Q fever. METHODS: We investigated gene expression of MMPs through microarray analysis and MMP production with ELISA in C. burnetii-stimulated peripheral blood mononuclear cells (PBMCs) of patients with chronic Q fever and healthy controls. Twenty single nucleotide polymorphisms (SNPs) of MMP and tissue inhibitor of MMP genes were genotyped in 139 patients with chronic Q fever and 220 controls with similar cardiovascular co-morbidity. Additionally, circulating MMPs levels in patients with chronic Q fever were compared with those in cardiovascular controls with and without a history of past Q fever. RESULTS: In healthy controls, the MMP pathway involving four genes (MMP1, MMP7, MMP10, MMP19) was significantly up-regulated in C. burnetii-stimulated but not in Escherichia coli lipopolysaccharide -stimulated PBMCs. Coxiella burnetii induced MMP-1 and MMP-9 production in PBMCs of healthy individuals (both p<0.001), individuals with past Q fever (p<0.05, p<0.01, respectively) and of patients with chronic Q fever (both p<0.001). SNPs in MMP7 (rs11568810) (p<0.05) and MMP9 (rs17576) (p<0.05) were more common in patients with chronic Q fever. Circulating MMP-7 serum levels were higher in patients with chronic Q fever (median 33.5 ng/mL, interquartile range 22.3-45.7 ng/mL) than controls (20.6 ng/mL, 15.9-33.8 ng/mL). CONCLUSION: Coxiella burnetii-induced MMP production may contribute to the development of chronic Q fever.

Coxiella burnetii: the 'query' fever bacterium. A model of immune subversion by a strictly intracellular microorganism.

Although substantial progress occurred in the knowledge of Coxiella burnetii during the past years, the pathophysiology of Q fever is still obscure. Emerging evidence from clinical investigations suggested that certain disorders of cell-mediated immunity play a pivotal role in Q fever and especially in its chronic form. This review analyses the potential strategies that C. burnetii, a strictly intracellular pathogen, use to divert microbicidal mechanisms of macrophages and to depress protective T-cell mediated immunity. The role of monocytes in the induction of Q fever is specifically discussed.

Self-limitation of the oxidative burst of rat polymorphonuclear leukocytes.

The oxidative response of rat polymorphonuclear leukocytes stimulated by phorbol myristate acetate and N-formyl-methionyl-leucyl-phenylalanine was studied. Ferricytochrome reduction and peroxidase-catalyzed decrease of scopoletin fluorescence were used to monitor O-2 and H2O2 release in the extracellular medium. Oxygen consumption was also measured in some experiments. Decrease of chlortetracyclin fluorescence after stimulation of dye-loaded cells was used to study an early step of cell stimulation. Finally, a possible relationship between cell responses and the medium redox potential was explored. Three major conclusions were obtained: Ferricytochrome reduction is dependent on the total cytochrome concentration, and a simple mathematical model allows a tentative estimate of total superoxide anion production by stimulated cells. Increasing cell concentration results in a decrease of individual cell response, and this may be accounted for by a direct inhibition of cell-released hydrogen peroxide on the reactivity of leukocytes. Further, H2O2 may be shown to inhibit an early step of cell response. The solution redox potential does not influence cell reactivity, since it may be dramatically decreased without inhibiting cell response.

Effect of granulocyte-macrophage colony-stimulating factor on superoxide production in cytoplasts and intact human neutrophils: role of protein kinase and G-proteins.

Granulocyte-macrophage colony-stimulating factor, GM-CSF, potentiates superoxide generation produced by human neutrophils stimulated with fMet-Leu-Phe and platelet-activating factor, PAF, but not by phorbol 12-myristate 13-acetate (PMA) or opsonized zymosan. The potentiation is greatest in fMet-Leu-Phe-stimulated cells. This indicates that the actions of only certain receptors are potentiated by GM-CSF. Incubation of the cells with the protein kinase inhibitor H-7 or with the protein synthesis inhibitor cyclohexamide before the addition of GM-CSF does not affect the observed potentiation. The rationales behind these studies are to examine the roles of protein kinase C and protein synthesis in the action of GM-CSF. The data suggest that neither protein kinase C nor protein synthesis is necessary for GM-CSF action. On the other hand, no potentiation can be seen in the presence of cytochalasin B. Unlike intact cells, GM-CSF does not enhance superoxide production by cytoplasts stimulated with fMet-Leu-Phe. The rationale behind the use of cytoplasts is to examine the role of granules and/or nucleus in GM-CSF action, and the data indicate that one or more of these two components is necessary for the priming effect of GM-CSF. The amount of actin associated with the cytoskeleton under control of fMet-Leu-Phe-stimulated condition is the same in normal and GM-CSF-treated human neutrophils. Botulinum D toxin ADP-ribosylates a protein with a molecular weight of 22 kDa. This ribosylation is reduced in homogenates obtained from cells pretreated with botulinum D toxin or GM-CSF. Botulinum D toxin does not affect the basal or the fMet-Leu-Phe-induced rise in the intracellular concentration of free calcium in human neutrophils. GM-CSF also increases the rise in intracellular concentration of free calcium in human neutrophils stimulated with PAF or fMet-Leu-Phe. The increases are inhibited by pertussis toxin. Several important conclusion can be drawn from these data. 1) GM-CSF potentiates the rise in Ca2+i produced by PAF and fMet-Leu-Phe, and these potentiations are inhibited in pertussis-toxin-treated cells. 2) GM-CSF does not prime cytoplasts to stimulation by fMet-Leu-Phe. This suggests that the granules and/or nucleus are necessary for the priming action. 3) The priming by GM-CSF is not mediated by the H-7-sensitive protein kinase C, botulinum D-sensitive G-protein, or protein synthesis.

Myotonic dystrophy: defective oxidative burst of polymorphonuclear leukocytes.

Because myotonic dystrophy (MD) is an autosomal dominant multisystemic disorder affecting plasma membrane, we have studied the oxidative burst of PMNs. The PMA and fMet-Leu-Phe-stimulated superoxide generation is defective in the patient group as compared to controls: the response is both delayed and low. The kinetic parameters of the NADPH oxidase complex are not affected. We have not found any abnormalities in the membrane potential changes. In addition, the cytosolic protein kinase C (PKC) activity of resting PMNs is similar in MD patients and controls, and the translocation of protein kinase C in response to PMA is not impaired. The decrease of the oxidative response of PMNs from MD patients may be related to an abnormality of the environment of the NADPH oxidase.

Legionella pneumophila inhibits superoxide generation in human monocytes via the down-modulation of alpha and beta protein kinase C isotypes.

Legionella pneumophila may subvert monocyte defenses by several mechanisms including the inhibition of phagosome-lysosome fusion or the impairment of oxidative metabolism. We have investigated the effect of L. pneumophila Knoxville 1, a virulent strain that does not inhibit phagosome-lysosome fusion, on the oxidative responsiveness of human monocytes. Infection of monocytes with L. pneumophila for 48 h resulted in marked inhibition of superoxide generation stimulated by phorbol myristate acetate (PMA) but not by zymosan, a particulate agonist. Evidence is provided that L. pneumophila interfered with the transductional pathway (i.e., protein kinase C, PKC) leading to activation of the NADPH oxidase in monocytes. The phosphorylation of 34-, 48-, 62-, 68-, and 80-kDa proteins stimulated by PMA was markedly inhibited in infected monocytes. In addition, the expression of both alpha and beta PKC isotypes was partially inhibited in infected monocytes. Taken together, our data suggest that the down-modulation of PKC isotypes plays a role in the inhibition of PMA-stimulated superoxide generation.

Phagocytic cell function in aged subjects.

In order to study the activity of phagocytic cells in normal and pathological aging, we compared normal young and aged subjects and patients with Alzheimer's (AD) or Parkinson's (PD) disease. Blood granulocytes and monocytes were separately assayed for ingestion of three different particle species (opsonized zymosan, immunoglobulin-coated sheep red cells (IgG-SRC) and glutaraldehyde-treated sheep red cells (G-SRC]. The superoxide anion production induced by these particles was also measured. All granulocyte responses to zymosan and IgG-SRC were depressed in the three aged groups as compared to young controls. Hence, only functions involving a specific receptor (Fc or C3b receptor) seemed affected. Monocyte activity was slightly decreased in the same groups. No difference was found between AD or PD patients and normal aged subjects. Hence the phagocytic and oxidative defects we found were a consequence of aging.

Study of cell deformability by a simple method.

Cell deformability plays an important role in many immunological processes, such as phagocyte chemotaxis and endocytosis. The most widely used method of assay consists in aspirating cells into glass micropipettes and measuring the length of the protrusion induced by a given pressure, or the minimum pressure required to drive cells into the micropipette. This procedure requires specialized equipment and delicate manipulation. The present report describes a simpler procedure: cells are centrifuged in petri dishes floating on a water cushion, then fixed and coated with 0.8 micron diameter latex beads, which allows rapid and accurate determination of their height. This method is compared with the micropipette technique by studying lymphocyte and macrophage-like cell lines in physiological medium and in the presence of a divalent cation chelator or a microfilament inhibitor. In addition to simplicity, the main advantages of this technique are that (i) many cells may be examined within a reasonable period of time, which allows testing of heterogeneous cell populations, and (ii) unexpectedly, centrifugation was quite harmless under our experimental conditions, since it did not impair cell proliferative ability nor phagocytic ability. It is concluded that the method may be used in clinical laboratories to explore phagocyte dysfunctions, as well as in experimental studies.

Intrapulmonary production of RANTES during rejection and CMV pneumonitis after lung transplantation.

RANTES (regulated upon activation, normally T expressed and secreted) is a chemoattractant for macrophages, memory T lymphocytes, and eosinophils. We investigated whether intrapulmonary production of the chemokine RANTES contributes to the recruitment of immune cells during lung transplantation complications. RANTES concentration was measured in bronchoalveolar lavage (BAL) fluids using an ELISA assay. It was significantly higher during CMV pneumonitis (36.2 +/- l6 pg/ml, n=12, P=0.031) and allograft rejection (31.1 +/- 8.5 pg/ml, n=27, P=0.013) than in patients without complications (9.1 +/- 2.3 pg/ml, n=22). At least some of the RANTES was produced by lung macrophages: BAL macrophages cultured for 24 hr spontaneously released larger amount of RANTES during CMV pneumonitis (140 +/- 53 pg/ml, n=8, P=0.002) and allograft rejection (84 +/- 44 pg/ml, n=11, P=0.037) than in control patients (15.2 +/- 6.5 pg/ml, n=21). Moreover, macrophages in transbronchial biopsies were labeled by an anti-RANTES mAb. RANTES production by BAL macrophages was followed in 2 patients with CMV pneumonitis. It remained high as long as CMV-induced cytopathic effects or clinical symptoms were present, but it returned to baseline as the infection was controlled. These results suggest that the intrapulmonary production of the chemokine RANTES by activated macrophages contributes to the intrapulmonary accumulation of immune cells during complications of lung transplantation.

Elevated circulating levels of IL-6 in schizophrenia.

Schizophrenia may result from immune or inflammatory disorders, which are mediated by cytokines. Data in this field are heterogeneous and often contradictory. We investigated circulating levels of IL-6 and TNF-alpha, two distinct proinflammatory cytokines. Using immunoassay, we assessed IL-6 and TNF-alpha in serum from chronic schizophrenic patients (n = 30) and normal controls (n = 15). Circulating levels of IL-6 were higher in patients than in controls; those of TNF-alpha were not significantly higher than in controls. In addition, IL-6 levels were higher in patients with acute exacerbation of schizophrenia than in patients with remissions. Our results suggest that immunologic abnormalities in schizophrenia may be related to a specific inflammatory process mediated by IL-6. An interesting line of research would be the evaluation of IL-6 cerebral production in CSF.