👤 Vivekanandhan Aravindhan

Childhood exposure to filariasis can confer significant protection against diabetes which is called as "Metabolic Hygiene Hypothesis". However, the effect of diabetes on anti-filarial immunity is not much studied. In the present study, the role of diabetes on systemic anti-filarial immunity was elucidated. Plasma levels of innate immune cytokines, adaptive immune cytokines, chemokines, hormones and growth factors were quantified by ELISA; Lipid and protein peroxidation and nitrite levels were quantified by spectrophotometry; Peripheral Tregs and exhausted T-cells were quantified by flowcytometry; FoxP3 expression was quantified by qRT-PCR. Anti-filarial immunity was significantly associated with elevated levels of TNF-α, IL-6, IL-1β, IL-10, IL-1Ra, DEF-A1, IL-12, IFN-γ, IL-2, IL-33, IL-9, IL-23, IL-17, IL-8, IP-10, SDF-1, MCP-1 and RANTES and decreased levels of IL-27, IL-4, leptin and FGF-21. Lipid peroxidation, nitrite levels and exhausted T cells were also increased. Chronic diabetes significantly reduced IL-1β, IL-1Ra, DEF-A1 and IL-8 and lipid peroxidation, and increased VEGF levels in DM-LF group. Overall, diabetes was found to downregulate a few critical innate immune components, of anti-filarial immunity, that can promote chronic pathology in LF + subjects. Show less

Polycystic ovary syndrome (PCOS) is a common metabolic/ endocrine disorder seen predominantly in women in their reproductive age, which increases the risk of infertility, endometrial cancer and metabolic disorders. IL-27 and IL-38 are recently discovered, novel anti-inflammatory cytokines whose role in immune-endocrine dysfunction seen in PCOS is largely unknown. In the present study, we quantified these two cytokines along with markers for meta-inflammation (TNF-α, IL-6, IL-1β, IL-1Ra, IL-10 and TGF-β) and hormonal dysregulation (insulin, leptin, adiponectin, FGF-21, testosterone and DHEA-S) in the serum of PCOS women (n=44), along with age matched controls (n=20), by ELISA. We quantified serum lipid peroxidation, protein peroxidation, and nitrite levels using spectrophotometry. PCOS women had significantly elevated levels of IL-27, IL-38 along with TNF-α, IL-6, IL-1Ra, IL-10, FGF-21 and adiponectin, and decreased levels of TGF-β, SDF-1 and leptin. While there is no significant difference with respect to redox markers, nitrite levels were significantly increased in PCOS cases. The increased circulating levels of anti-inflammatory cytokines IL-27 and IL-38 under PCOS conditions warrant further investigation. To the best of our knowledge, this is the first report on IL-38 levels in PCOS. Show less

Metainflammation, as seen in chronic diabetes subjects, impairs immunity and increases the susceptibility to infections. In the present study, the effect of diabetes on immune response against filariasis was studied. Both toll-like receptor (TLR)-mediated and crude antigen-induced immune responses were quantified, in whole blood cultures from filariasis-infected subjects (LF+), with and without diabetes. Blood cultures were stimulated with TLR ligands (TLR2 and TLR4) or filarial antigen or were left unstimulated (control) for 18 h. Cytokine, chemokine, and defensin secretion was quantified by ELISA. Expression of HLA-DR, B7-1, B7-2, activation marker (CD69), and Th (Th1, Th2, Th17, and Th9) phenotypes was quantified by flow cytometry. Expression of immunomodulatory effectors (Cox-2, HO-1, IDO-1, and p47Phox) and Th-polarizing transcription factors (T-bet, GATA3, and ROR-γt) was quantified by quantitative PCR. Secretion of IL-27, IL-1Ra, IL-12, IL-33, IL-9, and SDF-1 was increased under diabetes conditions with increased Th9 polarization and increased expression of Cox-2 and IDO. Overall, diabetes was found to augment both TLR-mediated and antigen-induced inflammation, which can promote chronic pathology in LF+ subjects. Show less

Anti-inflammatory cytokines act as double edged swords- they can dampen inflammation but can also suppress immunity. The role played by these cytokines in latent TB infected (LTBI) subjects, with various grades of glucose intolerance was studied. Both serum levels and recall-secretion of IL-27, IL-10, IL-1Ra and TGF-β in Normal Glucose Tolerance (NGT), Pre-Diabetes (PDM), Newly diagnosed Diabetes (NDM) and Known Diabetes (KDM) subjects, both with and without LTBI (n = 382), were quantified by ELISA. All the subjects were screened for LTBI by QuantiFERON-TB Gold test. Serum levels of IL-27, IL-10 and IL-1Ra were significantly elevated in the LTB Show less