Introduction Type 2 cytokines such as IL-13, IL-4 and IL-5 have been shown to play important roles in the pathogenesis of asthma. One source of these cytokines is type 2 CD4 +or CD8+T cells. We have shown that epithelial cells have inhibitory effects on these T cells and that this regulatory effect could be defective in asthma. We have previously shown that type 2 T cell lines release less IL-13 in the presence of epithelial cells and others have shown that epithelial cells are able to reduce division of CD4 +T cells. We wished to extend these studies to determine whether bulk cultures of PBMC were able to release IL-13 and whether this IL-13 was regulated by epithelial cells and whether this was mediated by direct cell contact.

Methods We used PBMC from healthy donors and cultured cells in the presence and absence of epithelial cells with titrated doses of IL-2. We used transwells and epithelial cell supernatants to determine whether supernatants were also able to reduce type 2 cytokine secretion. We used size exclusion centrifugation to split supernatants into different fractions.

Results After culture of PBMC for 5 days in IL-2, IL-13 release (pg/10⁶ cells+/-SD) was 509.95+/-84.95 and was reduced to 37.3+/-7.4 by A549 epithelial cells separated by a transwell. Titration of A549 cells established that inhibition was cell number dependent. Inhibition was not due to scavenging of IL-13 by epithelial cells during co-culture. Less IL-13 was secreted by IL-2 treated PBMC (pg/10⁶ cells+/-SD) in the presence of 50% v/v supernatant from healthy HBEC 49+/-7 or asthma HBEC 90+/-21 p=0.0023. IL-5: HHBEC 14+/-5 AHBEC 26+/-12 not significant. Splitting the HBEC supernatant into different size fractions showed that the fraction over 3 kD was less inhibitory than the fraction under 3 kD.

Conclusion There may be a soluble mediator secreted by epithelial cells that is less than 3 kDa in mass that is able to inhibit type 2 cytokine release from PBMC. These inhibitory factor(s) could contribute to the regulation of type 2 cells that and affect asthma pathogenesis.