MODULATION OF COMEDONAL LEVELS OF INTERLEUKIN-1 IN ACNE PATIENTS TREATED WITH TETRACYCLINES

To understand the basis for the anti-inflammatory activity 0 tetracycl ines in acne, we compared the cytokine profiles [interleukin 1 (IL-1) alpha and beta, tumor necrosis factor (TNF) alpha, and IL-6] and bacte rial flora of 66 open comedones removed from eleven patients before an d after at least 8 weeks treatment with either tetracycline or minocyc line. Pre-treatment, the only cytokine regularly recovered from comedo nes was bioactive IL-1alpha-like material. The mean concentration of I L-1alpha-like bioactivity/mg comedonal material rose from 272.0 +/- 88 .6 pg to 844.3 +/- 196.7 pg following treatment (p < 0.05, Wilcoxon ma tched pairs). All six minocycline-treated patients showed an increase in bioactive IL-1alpha-like material compared with three of five tetra cycline-treated patients. The incidence (p < 0.001, chi2) and concentr ation (p < 0.05, Wilcoxon) of immunochemical IL-beta were also raised post-treatment, although significantly more patients assigned to minoc ycline therapy had detectable levels of this cytokine before therapy w as initiated. However, the mean concentration of IL-1beta/mg comedonal material post-treatment was similar in both groups (72.5 +/- 23.3 pg for tetracycline-treated compared with 78.6 +/- 41.9 pg for minocyclin e-treated patients). The other cytokines were either absent (IL-6) or present in < 10% of comedones (TNFalpha) before and after therapy. Fol lowing treatment, only three of 11 patients showed a decrease of great er-than-or-equal-to 1 log10 in propionibacterial numbers/mg comedonal material, whereas six patients showed an increase of > 0.5 log10 in nu mbers of staphylococci. In eight patients, the increase or decrease in staphylococcal numbers correlated with the change in concentration of IL-1alpha-like bioactivity. This is the first study to show an effect of antibiotic therapy on cytokine levels in vivo. Increased levels of IL-1 in comedones destined to become inflamed may enhance resolution and promote repair of the damaged follicular epithelium. Hence, these results provide further evidence of the augmentation of immune respons es by tetracyclines and support the hypothesis that epidermal IL-1 pla ys a physiologic role in wound healing.