This study was performed to evaluate the transcriptional regulation of interleukin-4 (IL-4) on collagen gene expression in systemic sclerosis (SSc) fibroblasts. The pro alpha 2(I) collagen promotor activity has been examined by transfection experiments and chloramphenicol acetyl transferase (CAT) assay. Maximal elevation of collagen synthesis was presented at a concentration of 5 ng/ml of IL-4. In the CAT assay, the percentage of acetylation was 7.0% +/- 2.0% in untreated controls and 12.5% +/- 3.5% in SSc fibroblasts at 5.0 ng/ml of IL-4. In normal skin (NS), 3.5% +/- 1.0%, and 10.2% +/- 2.5% were acetylated, respectively. The promoter activity was increased 1.8 +/- 0.7-fold and 2.9 +/- 1.3-fold in IL-4-treated SSc and NS, respectively, as compared to untreated groups. In Northern and dot-blot analysis, the level of types I and III collagen mRNA increased 1.1 +/- 0.3-fold and 1.3 +/- 0.3-fold, respectively, in IL-4-treated SSc fibroblasts compared to 3.0 +/- 0.4-fold and 3.0 +/- 0.3-fold, respectively, in NS fibroblasts. These data may indicate that IL-4 could be important in promoting biogenesis of collagen proteins by increased stability and transcription of the collagen mRNA. Also, transcriptional activation of collagen gene expression appears to have a less sensitive effect on SSc than on NS.