Role of Cytokines in Experimental and Human Visceral Leishmaniasis

Abstract

Visceral Leishmaniasis (VL) is the most fatal form of disease leishmaniasis. To date, there are no effective prophylactic measures and therapeutics available against VL. Recently, new immunotherapy-based approaches have been established for the management of VL. Cytokines, which are predominantly produced by helper T cells (Th) and macrophages, have received great attention that could be an effective immunotherapeutic approach for the treatment of human VL. Cytokines play a key role in forming the host immune response and in managing the formation of protective and non-protective immunities during infection. Furthermore, immune response mediated through different cytokines varies from different host or animal models. Various cytokines viz. IFN-γ, IL-2, IL-12, and TNF-α play an important role during protection, while some other cytokines viz. IL-10, IL-6, IL-17, TGF-β, and others are associated with disease progression. Therefore, comprehensive knowledge of cytokine response and their interaction with various immune cells is very crucial to determine appropriate immunotherapies for VL. Here, we have discussed the role of cytokines involved in VL disease progression or host protection in different animal models and humans that will determine the clinical outcome of VL and open the path for the development of rapid and accurate diagnostic tools as well as therapeutic interventions against VL.

Multifunctional, TNF-α and IFN-γ-Secreting CD4 and CD8 T Cells and CD8High T Cells Are Associated With the Cure of Human Visceral Leishmaniasis

“…On the other hand, the IL-6 cytokine, which is associated with severity and death of VL, was related to the impairment of TNF-a secretion soon after infection and to the consequent inhibition of Th1 response (36,42,43). In fact, TNF-a is associated with the activation of effector immune responses (42), and the TNF-a levels only returned to normal after the anti-Leishmania therapy, which correlated with clinical cure (44).…”

“…However, this production of IFN-g was decreased by the impairment of the (HLA)-DR antigen, suggesting that it is mediated by a typical HLA-TCR receptor association. Moreover, and in spite of the progressive immunosuppression of VL, an intrinsic IFN-g produced by patients helped to control the expansion of the parasites (41), and the lack or diminished production of IFN-g determines the patient vulnerability to VL (42). On the other hand, the IL-6 cytokine, which is associated with severity and death of VL, was related to the impairment of TNF-a secretion soon after infection and to the consequent inhibition of Th1 response (36,42,43).…”

“…Moreover, and in spite of the progressive immunosuppression of VL, an intrinsic IFN-g produced by patients helped to control the expansion of the parasites (41), and the lack or diminished production of IFN-g determines the patient vulnerability to VL (42). On the other hand, the IL-6 cytokine, which is associated with severity and death of VL, was related to the impairment of TNF-a secretion soon after infection and to the consequent inhibition of Th1 response (36,42,43). In fact, TNF-a is associated with the activation of effector immune responses (42), and the TNF-a levels only returned to normal after the anti-Leishmania therapy, which correlated with clinical cure (44).…”

Psychological Stresses in Children Trigger Cytokine- and Kynurenine Metabolite-Mediated Abdominal Pain and Proinflammatory Changes

“…The lower concentrations of TNF-α in this study cohort of children with parasitic infections may be due to their significantly higher concentrations of IL-10. IL-10, a cytokine with broad immunoregulatory function, is known to inhibit the production of iNOS, IFN-γ, IL-12, TNF-α production and suppresses parasite killing in a variety of protozoan and helminth infections ( 59 , 60 ). In addition, these cohort of children also showed increased concentrations of a pleiotropic cytokine, IL-6.…”

“…This may be due to its immunosuppressive effect as well as regenerative effect as IL-6-dependent mucosal protection was demonstrated in enteric bacterial pathogen ( 61 ). Together, the impact of IL-10 and IL-6 modulated immunosuppression is found to be beneficial and could contribute the apparently healthy status in them ( 60 ).…”