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Comment on "Misoprostol Impairs Female Reproductive Tract Innate Immunity against Clostridium sordellii"

Gynuity Health Projects, New York, NY 10010

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 intrauterine 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 allow us to conclude that vaginal administration would result in higher endometrial concentrations of misoprostol than would occur following other routes of administration.

Second, the bacteria were introduced via the uterus and the uterine horn was subsequently tied off, a model that does not mimic the presumed nature of pelvic infection with Clostridium 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 8–10 h (2). Yet, among the reports of C. sordellii infections among women, women presented with symptoms 3–5 days following misoprostol exposure.

Fourth, caution is warranted when applying results from nonhuman 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 nonvaginal misoprostol administration (4). The estimated relative risk among women taking misoprostol vaginally and nonvaginally 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 highlights the important duty that scientists have in explaining and interpreting research so that advocates and media can report on them responsibly.

References

1. Aronoff, D. M., Y. Hao, J. Chung, N. Coleman, C. Lewis, C. M. Peres, C. H Serezani, G.-H. Chen, N. Flamand, T. G. Brock, M. Peters-Golden. 2008. Misoprostol impairs female reproductive tract innate immunity against Clostridium sordellii. J. Immunol. 180: 8222-8230. [Abstract/Free Full Text]
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: 288-294. [Medline]
3. Mestas, J., C. C. W. Hughes. 2004. Of mice and not men: differences between mouse and human immunology. J. Immunol. 172: 2731-2738. [Abstract/Free Full Text]
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, et al 2007. Toxic shock associated with Clostridium sordellii and Clostridium perfringens after medical and spontaneous abortion. Obstet. Gynecol. 110: 1027-1033. [Medline]

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