Experimental assessment of immunobiological activity of the roncoleukine immunomodulatory agent
- O. I. Mamykova
- Russian Agricultural Sciences
Distinct phenotypic outcomes following infection of mice with Leishmania major are closely linked to the emergence of functionally dissimilar Th1 or Th2 CD4+ T-cell responses early in the course of disease. This model of T-cell-dependent microbial pathology has proven useful for the study of cytokine regulatory and effector functions in vivo. To this end, the causal relationships linking synthesis of IFN gamma to cure and of IL4 to disease exacerbation have already been well characterized. IL12 also has a defined role in shaping the immune response against L. major. Early treatment with recombinant IL12, or vaccination using IL12 as an adjuvant, protects genetically susceptible hosts from progressive infection. Protective mechanisms include both suppression of deleterious Th2 cell responses and amplification of beneficial Th1 cell activities. Although Leishmania are poor stimuli for macrophage-derived IL12 when compared to bacteria and other protozoa, in vivo production during infection can be indirectly demonstrated by the worsening of leishmaniasis that follows anti-IL12 injection in normally resistant mice. Whether IL12 production during infection represents constitutive or regulated synthesis by infected macrophages is unresolved and deserves further exploration.