Interleukin 4 and 13 participation in mycobacterial (type-1) and schistosomal (type-2) antigen-elicited pulmonary granuloma formation: Multiparameter analysis of cellular recruitment, chemokine expression and cytokine networks

The contribution of IL-4 and IL-13 to inflammation and cytokine responses was compared in mice with types-1 or -2 pulmonary granulomas (GR) elicited by beads bound to antigens of Mycobacteria bovis (PPD) or Schistosoma mansoni eggs (SEA). Type-2 SEA-GR produced the most IL-4 and IL-13, Type-1 PPD-GR produced detectable IL-13, but not IL-4, Mice were treated with anti-IL-4 or anti-IL-13 Abs, then lesion size/composition, cytokine/chemokine mRNA and lymph node cytokines were measured, Type-1 GRs resisted individual Abs, but combined Abs augmented lesions by 20%. In contrast, anti-IL-4 abrogated type-2 GR by 30-40% and eosinophil recruitment by 60%. Anti-IL-13 abrogated type-2 GR by 20-30% with no effect on eosinophils, Combined depletion reduced lesion area by 60% and eosinophils by more than 80%, In type-1 GR lungs, anti-IL-4 and anti-IL-13 augmented IFN gamma and TNF alpha mRNA, In type 2 lungs, anti-IL-13 did likewise, but anti-IL-4 decreased TNFa without affecting IFN gamma mRNA, In both responses, IL-4 promoted MCP-1 and MCP-5 mRNA, but IL-13 inhibited chemokines in type-1 GR, In lymph nodes, anti-IL-4, but not anti-IL-13, abrogated type-2 cytokines, In fact, IL-13 down-regulated itself and other type-2 cytokines. In summary, IL-4 and IL-13 have common and disparate regulatory functions in types 1 and 2 responses. (C) 2000 Academic Press.