Interleukin (IL)–12 and IL-23 Are Key Cytokines for Immunity against Salmonella in Humans

Patients with inherited deficiency of the interleukin (IL)–12/IL-23–interferon (IFN)–g axis show increased susceptibility to invasive disease caused by the intramacrophage pathogens salmonellae and mycobacteria. We analyzed data on 154 patients with such deficiency. Significantly more patients with IL-12/IL-23–component deficiency had a history of salmonella disease than did those with IFN-g–component deficiency. Salmonella disease was typically severe, extraintestinal, and caused by nontyphoidal serovars. These findings strongly suggest that IL-12/IL-23 is a key cytokine for immunity against salmonella in humans and that IL-12/IL-23 mediates this protective effect partly through IFN-g–independent pathways. Investigation of the IL-12/IL-23–IFN-g axis should be considered in patients with invasive salmonella disease

Neutrophil and lymphocyte responses to oral Streptococcus in Adamantiades-Behcet's disease

Immune reactions against microorganisms play an important pathogenic role in Adamantiades-Behçet’s disease (ABD). We had previously obtained Streptococcus sanguinis (strain BD113-20) isolated from the oral cavity of patients with ABD. To investigate the pathogenesis of this isolate, we examined neutrophil 5 reactions and level of cytokine production by lymphocytes after stimulation with the strain. The reactions of neutrophils were examined by chemiluminescence assay using whole blood. The amounts of interferon gamma (IFN-g) and interleukin (IL)-4, IL-8, IL-10, and IL-12 produced by peripheral blood mononuclear cells (PBMCs) were measured by ELISA. 10 Strain BD113-20 activated neutrophils from patients with ABD and healthy volunteers, and, in addition it increased IFN-g production by lymphocytes. Lymphocyte from the patients with ABD showed a dominant T helper 1 (Th-1) immune response. Results indicated that both bacterial stimulation and host hypersensitivity might be involved in the symptoms and pathogenesis of ABD

The Emerging Roles of Human Immunity-Related GTPase M (IRGM) Gene

Immunity-related GTPase family M (IRGM) protein, discovered for the first time in 1990, belongs to IRG family of proteins and is divided into five subfamilies (IRGA, IRGB, IRGC, IRGD and IRGM). These are responsive to interferon-g and play a pivotal role in immune response to pathogens in mice. Owing to lack of interferon response element in the promoter region, human IRGM does not respond to interferon-g stimulation, which is why it was earlier thought to be non-functional gene. Moreover, evolutionary history suggests that this gene was non-functional for ~25 million years ago. Bioinformatics has been instrumental in elucidating its evolutionary history as well as functions, especially in its interactions with the proteins of autophagy pathway.  Recently, several studies have demonstrated the various functions of IRGM in limiting different pathogens in humans. This review discusses how and various roles played by IRGM unraveled in the recent years

Nutrition and immunity : the effects of the combination of arginine and tryptophan on growth performance, serum parameters and immune response in broiler chickens challenged with infectious bursal disease vaccine

To explore the effects of the combination of tryptophan (Trp) and arginine (Arg) on growth performance, serum parameters and immune response of broiler chickens challenged with intermediate plus strain of infectious bursal disease virus vaccine, an in vivo experiment was conducted. A corn-soybean meal-based diet containing different levels of Arg and Trp was used. Cobb500 male broiler chickens from 0 to 49 days of age were subjected to a diet supplemented with the combination of Trp and Arg. Growth performance parameters and serum parameters were measured at 27 and 49 days of age. To evaluate the immunomodulatory effects of the combination of Trp and Arg on the challenged chickens, we measured the serum levels of interferon-α, interferon-γ and immunoglobulin G at 27, 35, 42, and 49 days of age. The results showed that the three evaluated immune system parameters including interferon-α, interferon-γ and immunoglobulin G were significantly enhanced after treatment. This enhancement resulted in the recovery of infectious bursal disease virus-infected chickens compared with controls as confirmed by histopathological examinations. Moreover, serum parameters such as albumin and total protein increased, whereas the treatment decreased (P<0.05) the feed:gain ratio, aspartate amino-transferase, alkaline phosphatase, lactic dehydrogenase, triglyceride and cholesterol. These findings suggest that the combination of Arg and Trp has a regulatory effect on growth performance. Moreover, it modulates the systemic immune response against infectious bursal disease

Correlation between a single nucleotide polymorphism (G/T at nt –88) in the Mx1 gene promoter and the response to interferon therapy for hepatitis C virus in Egyptian patients

Interferon used in the treatment of hepatitis C virus (HCV) patients stimulates the expression of a number of host genes encoding enzymes with antiviral activities, including myxovirus resistance gene- 1 (Mx1). Mx1 gene was found to have a single nucleotide polymorphism (SNP) at position -88 in the promotor region that affect the expression of Mx 1 protein and was suggested to be associated with the response of HCV. In this study, we assessed the relation between the SNP in the Mx1 gene and the responsiveness of Egyptian HCV patients to pegylated interferon and ribavirin treatment along with other host-related and virus-related predictors of treatment outcome. We genotyped the biallelic G/T SNP in the promoter region of Mx1 gene at position -88 from the transcription start site by restriction fragment length polymorphism (RFLP) in 42 interferon treatment-naïve Egyptian patients that were treated with pegylated interferon and ribavirin. We found that Mx1 nt-88 SNP is not significantly correlated to achieving sustained virological response (SVR) after pegylated interferon alpha and ribavirin combined treatment. We conclude that Mx1 gene polymorphism at codon nt-88 cannot be considered as biological marker to potentially identify responders and non-responders of HCV patients to achieve a sustained virological response to treatment with interferon (IFN) in combination with ribavirin.Key words: Hepatitis C virus (HCV), interferon (IFN), myxovirus resistance protein (Mx1 protein), myxovirus resistance gene-1 (Mx1 gene), single nucleotide polymorphism (SNP)

Erratum

Response to alpha 2B interferon treatment in a haemodialysis patient with chronic hepatitis C. The complete list of authors contributing to the above letter should have appeared as follows: G. Barril, J. A. Schez Tomero, L. Garcia Buey, J. L. Motellon, C. Bernis and J. A. Trave