Immunomodulatory effects of tretinoin in combination with clindamycin.
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.


CONCLUSIONS
The combination of tretinoin and clindamycin phosphate can be expected to be very effective in acne therapy.
Wauben-Penris
P J
PJ
Yamanouchi Europe B.V. Research Laboratories, Leiderdorp, The Netherlands. wauben.nl@yamanouchi-eu.com
Cerneus
D P
DP
van den Hoven
W E
WE
Leuven
P J
PJ
den Brok
J H
JH
Hall
D W
DW
D000152:Acne Vulgaris / Q000188:drug therapy / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002273:Carcinogens / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000473:pathology; D002981:Clindamycin / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors; D015848:Interleukin-5 / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology; D007641:Keratolytic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D018089:Superantigens / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D014212:Tretinoin / Q000008:administration & dosage / Q000494:pharmacology*; D000093242:Interleukin-6 Inhibitors
D000276:Adjuvants, Immunologic; D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D002273:Carcinogens; D002981:Clindamycin; D007371:Interferon-gamma; D015848:Interleukin-5; D007641:Keratolytic Agents; D018089:Superantigens; D013755:Tetradecanoylphorbol Acetate; D014212:Tretinoin; D000093242:Interleukin-6 Inhibitors