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Immunomodulatory effects of tretinoin in combination with clindamycin
P J Wauben-Penris1, D P Cerneus, W E van den Hoven
1Yamanouchi Europe B.V. Research Laboratories, Leiderdorp, The Netherlands. wauben.nl@yamanouchi-eu.com
Background:
Since acne is a multifactorial skin disease, therapies affecting several etiologic factors can have a higher than expected effectiveness. A combination of the antibiotic clindamycin phosphate and the retinoic acid tretinoin was developed.
Objective:
Anti-inflammatory and immunomodulatory effects of tretinoin in vitro were studied on human keratinocytes and peripheral blood mononuclear cells (PBMCs). Effects of clindamycin phosphate on tretinoin effects were studied.
Methods:
Anti-inflammatory effects on keratinocytes were assessed using an in vitro model with PMA (phorbol ester)-stimulated A431 cells (human epidermoid carcinoma). Immunomodulatory effects were measured on superantigen (SEB) stimulated PBMCs.
Results:
Tretinoin showed very potent inhibition of PMA-stimulated IL-6 (interleukin 6) release by A431 cells. The addition of clindamycin phosphate did not interfere with this effect. Tretinoin very potently stimulated IL-5 release, and inhibited IFN gamma release by SEB-stimulated human PBMCs. This indicates an immunomodulatory effect, stimulating Th2, and inhibiting Th1 dominated responses. These features have been related to the healing of acne lesions. The addition of clindamycin phosphate did not interfere with the immunomodulatory effects of tretinoin.
Conclusion:
The combination of tretinoin and clindamycin phosphate can be expected to be very effective in acne therapy.