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The Mode of Action of Cyclosporin

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Summary

To try to explain the wide therapeutic range of cyclosporin A, we examined its effects on physiological functions of skin and responses to immunological and inflammatory stimuli during and before or after administration of 5 mg/kg/day of cyclosporin A in the treatment of various skin diseases.

Pilocarpine-stimulated, sweat rate (10 patients), sebum excretion rate (10), scalp hair growth rate (8) and epidermal proliferation in response to tape-stripping (7) were not affected by cyclosporin A; nail growth rate was unaltered in patients without psoriasis (12), but was significantly slowed by treatment in patients with psoriasis (7) who had abnormally rapid growth before treatment.

Induction of cell-mediated sensitisation to 2,4-dinitrochlorobenzene (DNCB) was inhibited by cyclosporin A treatment (22 patients), but 7 patients sensitised to DNCB before cyclosporin treatment reacted normally to DNCB challenge during treatment. The immediate hypersensitivity response to intradermal house dust mite antigen was increased during treatment in 8 patients with atopy.

Weal responses to histamine (9 patients) and compound 48/80 (12), the 24 hour erythemal response to ultraviolet B (UVB) irradiation (10) and the inflammatory response to topical leukotriene B4 (16) were not affected, but cyclosporin A produced a striking inhibition of anthralin inflammation (21).

Since the methods we used will have detected all but minor changes, we conclude that cyclosporin A has no gross physiological effects on the skin and is not cytostatic; hypertrichosis must be due to a prolonged hair cycle. Secondly, cyclosporin A (a) impairs induction of cell-mediated sensitisation in doses which permit some continued expression, but (b) increases immediate hypersensitivity. Thirdly, cyclosporin A has no general anti-inflammatory effect, but we have found a novel and specific inhibitory effect on anthralin inflammation, the mechanism of which may underlie some of its therapeutic effects. The therapeutic effect of cyclosporin A may not be due solely to its immune effects, and other activities such as the anti-inflammatory effect we found need further exploration.

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Authors and Affiliations

  1. Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4LP, UK

    C. S. Munro, E. M. Higgins, B. Ramsay, J. McLelland, J. M. Marks, P. S. Friedmann, P. M. Farr, J. Rees, S. Young, C. M. Lawrence, F. Humphreys & S. Shuster

  2. Department of Histopathology, Royal Postgraduate Medical School, London, UK

    R. Dover

Authors
  1. C. S. Munro
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  2. E. M. Higgins
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  3. B. Ramsay
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  4. J. McLelland
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  5. J. M. Marks
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  6. P. S. Friedmann
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  7. P. M. Farr
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  8. R. Dover
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  9. J. Rees
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  10. S. Young
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  11. C. M. Lawrence
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  12. F. Humphreys
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  13. S. Shuster
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Munro, C.S., Higgins, E.M., Ramsay, B. et al. The Mode of Action of Cyclosporin. Drug Invest 2, 1–9 (1990). https://doi.org/10.1007/BF03259395

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