Transgene-induced production of IL-4 alters the development and collagen expression of Th1 type pulmonary granulomas

A number of complex mechanisms regulate the size and ceuularity of granulomatous reaction, particularly cytokine production profiles. The formation of Th1 type lesions consist of primarily mononuclear cells, whereas Th2 type granulomas have an additional eosinophil component and appear to become more fibrotic. In the present study, Th1 (purified protein derivative; PPD) and Th2 (Schistosome egg antigen; SEA) type granulomas were established to examine the role of IL-4 in lesion development. PPD-sensitized mice were transfected via the airway with an adenovirus construct containing an IL-4 cDNA cassette and the lungs embolized with Sephadex beads coated with PPD. The granuloma lesion size was significantly increased in the IL-4 transfected animals at days 2 and 5 compared to control groups. Furthermore, procollagen type III mRNA expression was significantly increased in the IL-4 transfected, PPD bead embolized lungs. In contrast, when IL-4 was neutralized during Th2 type SEA bead granulomas a significant decrease in procollagen type III was observed. These data indicate that the progression of certain granulomas may be regulated, in part, by the production of IL-4, thus altering the cellularity, size, and matrix composition of the inflammatory response.