Inhibition of Monocyte-Mediated Damage to Fungal Hyphae by Steroid Hormones

Abstract

Human monocytes can damage hyphal forms of C. albicans [1], R. oryzae [2], and A. fumigatus [3]. Because corticosteroids can inhibit phagocytosis and killing of bacteria by monocytes, the effects of steroid hormones on interactions of monocytes with hyphae were studied. Monocyte-mediated hyphal damage was inhibited by 10 microM hydrocortisone; inhibitory effects of lower concentrations of hydrocortisone were less marked with Rhizopus than with Candida or Aspergillus hyphae. Addition of 10% normal human serum to hyphae and monocytes did not affect the inhibitory effects of hydrocortisone (data not shown). Comparable inhibitory effects were obtained using 0.3-1.0 microM dexamethasone (data not shown). Estrogen and progesterone also inhibited damage to Candida or Rhizopus. However, inhibition occurred at concentrations which are readily achievable in vivo by pharmacologic doses of hydrocortisone, but not by other steroid hormones. Thus, pharmacologic doses of corticosteroids might produce serum hormone concentrations which could interfere with activity of host monocytes against the tissue-invasive forms of C. albicans and A. fumigatus in vivo. However, higher pharmacologic doses of these hormones may be required to inhibit leukocyte-mediated damage to Rhizopus hyphae. In contrast, predisposition of women to superficial candidal infections cannot be explained solely by direct effects of estrogens or progesterone on leukocyte-mediated hyphal damage.