The production of tumor necrosis factor alpha (TNF alpha) and interleukin 1 (IL-1) was measured in supernatants of cultured peripheral blood monocytes that were obtained from patients with human ...immunodeficiency virus type 1 (HIV 1) infection and that were purified by counterflow centrifugal elutriation (86-92% purity). TNF alpha levels were significantly higher in monocytes isolated from symptomatic HIV 1-infected patients as compared to normal controls. Although IL-1 levels were also elevated in this group of symptomatic patients they did not reach statistical significance. The production of the two monokines was intermediate in asymptomatic HIV 1-infected individuals. The increase of TNF alpha was observed in the absence of in vitro stimulation as well as in the presence of interferon-gamma plus lipopolysaccharide. TNF alpha and IL-1 were measured by radioimmunoassay and by bioassay, the results of the two methods being highly correlated for both cytokines. The levels of TNF alpha and IL-1 were also positively correlated. These data suggest that IL-1 and TNF alpha may be involved in the pathogenesis of HIV 1 infection.
The rumen harbors a complex microbial mixture of archaea, bacteria, protozoa, and fungi that efficiently breakdown plant biomass and its complex dietary carbohydrates into soluble sugars that can be ...fermented and subsequently converted into metabolites and nutrients utilized by the host animal. While rumen bacterial populations have been well documented, only a fraction of the rumen eukarya are taxonomically and functionally characterized, despite the recognition that they contribute to the cellulolytic phenotype of the rumen microbiota. To investigate how anaerobic fungi actively engage in digestion of recalcitrant fiber that is resistant to degradation, we resolved genome-centric metaproteome and metatranscriptome datasets generated from switchgrass samples incubated for 48 h in nylon bags within the rumen of cannulated dairy cows. Across a gene catalog covering anaerobic rumen bacteria, fungi and viruses, a significant portion of the detected proteins originated from fungal populations. Intriguingly, the carbohydrate-active enzyme (CAZyme) profile suggested a domain-specific functional specialization, with bacterial populations primarily engaged in the degradation of hemicelluloses, whereas fungi were inferred to target recalcitrant cellulose structures via the detection of a number of endo- and exo-acting enzymes belonging to the glycoside hydrolase (GH) family 5, 6, 8, and 48. Notably, members of the GH48 family were amongst the highest abundant CAZymes and detected representatives from this family also included dockerin domains that are associated with fungal cellulosomes. A eukaryote-selected metatranscriptome further reinforced the contribution of uncultured fungi in the ruminal degradation of recalcitrant fibers. These findings elucidate the intricate networks of in situ recalcitrant fiber deconstruction, and importantly, suggest that the anaerobic rumen fungi contribute a specific set of CAZymes that complement the enzyme repertoire provided by the specialized plant cell wall degrading rumen bacteria.
Objective. Patients with rheumatoid arthritis (RA) have defective hypothalamic responses to inflammation, possibly because of excessive production of cytokine inhibitor, which could blunt the effects ...of cytokines on the hypothalamus, or because of an imbalance between interleukin‐1β (IL‐1β) and interleukin‐1 receptor antagonist (IL‐1Ra), which could create a mainly proinflammatory state. The present study was undertaken to investigate these possibilities.
Methods. The in vivo kinetics of IL‐1β and IL‐1Ra secretion were studied in patients with RA, osteoarthritis (OA), and chronic osteomyelitis (OM), and in normal controls before and after surgery.
Results. The 24‐hour levels of IL‐1Ra were significantly increased in RA (P < 0.001), but there was no diurnal variation in any group. Preoperative levels of IL‐1Ra were higher in RA and OA sera (P = 0.001). After surgery, IL‐1Ra behaved like an acute‐phase reactant protein in all subjects. IL‐1β was 10–20 times higher in RA than in OM and OA patients at baseline, but the percentage increase in all groups postoperatively was the same. RA patients had an IL‐1Ra:IL‐1β ratio of 26.2 ± 3.7 (mean ± SEM) at baseline (OM patients 89.2 ± 5.8 and OA patients 1,310 ± 363); this increased to 66.5 ± 19.8 after surgery (OM patients 120 ± 6.7 and OA patients 325.8 ± 106).
Conclusion. RA patients have a dysregulation of IL‐1Ra production, and it seems unlikely that the defective hypothalamic response seen in RA is due to a functional deficit of IL‐1β.
Patients with cystic fibrosis suffer from a chronic, progressively destructive bronchitis characterized by colonization of the airways by Pseudomonas aeruginosa. Cell wall lipopolysaccharides from P. ...aeruginosa may stimulate secretion of cytokines such as tumor necrosis factor alpha (TNF alpha) by monocytes/macrophages. We found elevated levels of TNF alpha (150 +/- 60 pg/ml), interleukin-1 alpha (144 +/- 205 pg/ml), and interleukin-1 beta (62 +/- 100 pg/ml) in plasma from 25 patients with cystic fibrosis. In patients with less advanced disease, elevated plasma levels of TNF alpha correlated with high levels of complexes between neutrophil elastase and alpha 1-proteinase inhibitor, suggesting that TNF alpha may be a mediator of neutrophil degranulation. TNF alpha, by its chemotactic effect on neutrophils, may also contribute to the massive influx of neutrophils into and around the bronchial tree. Our findings raise the questions whether in patients with cystic fibrosis TNF alpha acts as cachectin and whether it mediates the anorexia that often results in weight loss.
ANCA are found in various systemic vasculitis and are supposed to play a role in the pathogenesis of the disease, in co-operation with other factors such as cytokines. A total of 36 ANCA-positive and ...10 ANCA-negative serum samples were analysed for the presence of TNF soluble receptors (TNF-sR), which are shed from the surface of activated cells and may act as TNF inhibitors. Of the ANCA-positive samples, 67% had elevated TNF-sR75 and 72% had elevated TNF-sR55 compared to ANCA-negative specimens (mean S.E. 18.7 17.3 vs 3.6 1.5 and 10.5 9.7 vs 1.9 0.7 ng/ml, P < 0.01). Elevation of TNF-sR in patients with ANCA suggests that cytokines and their inhibitors are involved in the pathogenesis of ANCA-associated autoimmune diseases.
In two groups of subjects at risk for acquired immune deficiency syndrome (AIDS), homosexual males and intravenous drug users with persistent generalized lymphadenopathy, humoral and cell-mediated ...immunity were compared. A small group of patients with definite AIDS were also studied. It was found that levels of immunoglobulins, serological markers for virus and other infections, cell-mediated immunity and histology of lymph nodes were similar in homosexuals and drug users, whereas the lymphocyte sub-populations differed completely. The number of T4+ lymphocytes was markedly decreased in homosexuals but normal in drug users; the number of T8+ lymphocytes was much higher in drug users than in homosexuals. This discrepancy may explain the extremely low prevalence of AIDS cases observed among Swiss drug users as compared with the high frequency noted among homosexuals.
PDF
