Decreased immunity after misprostol?
To all of you who have expressed concern about vaginal/buccal/oral misoprostol - a letter to the editor of the J. of Immunology that has been accepted for publication, by Beverly Winikoff, M.D., M.P.H., President, Gynuity Health Projects, New York , NY and her team.
To the Editor-in-Chief:
We read with interest the recent article by Aronoff, et al., published in The Journal of Immunology.[1] . The authors present data on the relationship between misoprostol exposure and the suppression of innate immunity in the rat. However, for the many reasons detailed below, we disagree strongly with their extrapolations to the effect of vaginal use of misoprostol for pregnancy termination in women.
First, in this study, misoprostol was not administered vaginally but via intra-uterine injection. We know of no study indicating that the local immune response of uterine tissue to direct misoprostol application is similar to what occurs following vaginal administration. Additionally, we have no data that allows us to conclude that vaginal administration would result in higher endometrial concentrations of misoprostol than following other routes of administration.
Second, the bacteria were introduced via the uterus and the uterine horn subsequently tied off, a model that does not mimic the presumed nature of pelvic infection with C. sordellii among women.
Third, the dose given to rats was nearly 20 times the standard dose used for pregnancy termination. In addition, the previously demonstrated immune response to misoprostol in humans given misoprostol orally lasted 8 to 10 hours.[2] Yet among the reports of C. sordellii infections among women, women presented with symptoms 3 to 5 days following misoprostol exposure.
Fourth, caution is warranted when applying results from non-human research to humans.[3] Moreover, the rats were not pregnant, an immune state markedly different from pregnancy.
Finally, there is no evidence that vaginal misoprostol use in women is uniquely responsible for the fatal toxic shock associated with medical abortion. A case was recently reported following non-vaginal misoprostol administration.[4] The estimated relative risk among women taking misoprostol vaginally and non-vaginally in the United States is nearly identical. In other countries, where vaginal misoprostol use is the standard of care for medical abortion, hundreds of thousands of women have used misoprostol vaginally without a single reported infection.
The potential for misconstruction and misuse of data highlights the important duty that scientists have in explaining and interpreting research so that advocates and media can report it responsibly.
Sincerely,
Caitlin Shannon, J.D., M.P.H., Beverly Winikoff, M.D., M.P.H.,
Senior Program Associate, President,
Gynuity Health Projects, New York NY Gynuity Health Projects, New York , NY
[1] Aronoff, D.M. Y. Hao, J. Chung, N. Coleman, C. Lewis, Peres CM, Serezani CH, Chen GH, Flamand N, Brock TG, Peters-Golden M. 2008. Misoprostol Impairs Female Reproductive Tract Innate Immunity against Clostridium sordellii. J. Immunol. 180: 8222-30.
[2] Waiser, J.T. Bohler, J. Stoll, B. Schumann, K. Budde, H-H. Neumayer. 2003. The immunosuppressive potential of misoprostol – efficacy and variability. Clin. Immunol. 109: 288-94.
[3] Mestas J. Hughes C.C.W. 2004. Of mice and not men: Difference between mounse and human immunology. J. Immunol. 172: 2731-8.
[4] Cohen A.L., J. Bhatnagar, S. Reagan, S.B. Zane, M.A. D'Angeli, M. Fischer, G. Killgore, T.S. Kwan-Gett, D.B. Blossom, W.J. Shieh, J. Guarner, J. Jernigan, J.S. Duchin, S.R. Zaki, L.C. McDonald. 2007. Toxic shock associated with Clostridium sordellii and Clostridium perfringens after medical and spontaneous abortion. Obstet. Gynecol. 110:1027-33.
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