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High Levels of Intrauterine Corticotropin-Releasing Hormone, Urocortin, Tryptase, and Interleukin-8 in Spontaneous Abortions

Department of Pharmacology and Experimental Therapeutics (B.M., D.K., S.C., W.B., T.C.T.), Tufts University School of Medicine, Boston, Massachusetts 02111; Department of Obstetrics and Gynecology (S.T.), InterBalkan Medical Center, Thessaloniki, 57001 Greece; Department of Obstetrics and Gynecology (V.K.), Aristotle University School of Medicine, Thessaloniki, 54124 Greece; Departments of Obstetrics and Gynecology (A.A.) and Internal Medicine (T.C.T.), Tufts-New England Medical Center, Boston, Massachusetts 02111

Address all correspondence and requests for reprints to: Theoharis C. Theoharides, Ph.D., M.D., Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, Massachusetts 02111. E-mail: theoharis.theoharides{at}tufts.edu.

Stress induces CRH secretion that activates hypothalamic-pituitary-adrenal axis and is also abortogenic. In addition to hypothalamus, CRH and its analog urocortin (Ucn) are also secreted locally outside the brain where they activate mast cells leading to inflammation; however, the level of CRH and Ucn or mast cell mediators has not been examined in products of conception (POC). CRH and Ucn were measured by enzyme immunoassay, tryptase by fluoroenzyme immunoassay, and IL-8 by ELISA in POC of 7-9 wk gestation from Caucasian women; they were divided into group I with elective abortions (n = 4), group II with one spontaneous abortion (n = 12), and group III with at least two spontaneous abortions (n = 7). CRH, Ucn, tryptase, and IL-8 levels were higher (P < 0.05) in group III (8683 ± 1201 pg/g, 7961 ± 1499 pg/g, 1553 ± 572 ng/g, and 8317 ± 1874 pg/g, respectively) than group II (2561 ± 314 pg/g, 2349 ± 394 pg/g, 403 ± 97 ng/g, and 3199 ± 449 pg/g, respectively) and group I (163 ± 162 pg/g, 328 ± 327 pg/g, 72 ± 31 ng/g, and 3681 ± 931 pg/g, respectively). Immunostaining of POC showed significantly more tryptase in group III women. High POC levels of CRH and Ucn under stress in habitual spontaneous abortions may activate uterine mast cells to secrete abortogenic tryptase and IL-8.

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