CYTOKINE FUNCTION DURING MYCOBACTERIAL AND SCHISTOSOMAL ANTIGEN-INDUCED PULMONARY GRANULOMA-FORMATION - LOCAL AND REGIONAL PARTICIPATION OFIFN-GAMMA, IL-10, AND TNF

Pulmonary granulomas (GR) with type 1 or type 2 cytokine involvement w ere induced in presensitized CBA mice by embolization of beads coupled to purified protein derivative (PPD) of Mycobacterium tuberculosis or soluble Ags derived from Schistosoma mansoni eggs (SEA). Using neutra lizing Abs against IFN-gamma, IL-10, and TNF-alpha/beta, we examined e ffects on GR size, GR macrophage function, and regional lymph node (LN ) responses. Profoundly different effects were observed in the two mod els. Anti-IFN decreased PPD-GR size by 20%, but augmented SEA GR by ne arly 50%. Anti-TNF abrogated PPD-GR area by 40% and SEA GR by 15% sugg esting that TNF contributed more to the former. Anti-IL-10 did not aff ect GR sizes. Analysis of TNF indicated that IFN was required for maxi mum production by both PPD GR and SEA GR macrophages. Interestingly, T NF tempered its own expression by SEA GR macrophages. In LN, PPD GR an d SEA GR formation was associated with T cell-dependent type 1 (IFN an d IL-2) and type 2 (IL-10 and IL-4) cytokine profiles, respectively. I n PPD LN, anti-IFN decreased IFN and IL-2 production by 50%. In contra st, anti-IL-10 increased IFN and IL-2 production by two- to fourfold, indicating that IFN and IL-10 had opposing effects on the type 1 respo nse. In SEA LN, anti-IFN decreased IFN production but augmented IL-4 a nd IL-10 production by 50 and 90%, respectively, supporting the notion that IFN constrains Th2 responses. Conversely, IL-10 promoted the Th2 response. Surprisingly, anti-TNF reduced IL-4 and IL-10 in SEA LN but did not affect PPD LN, suggesting that TNF-alpha or -beta supports Th 2 differentiation in LN during the secondary response to schistosomal Ags.