Dr. Mark Brown is an Assistant Professor within the Department of Pediatrics and the Arizona Respiratory Science Center (ARSC) at the University of Arizona. The ARSC is a multidisciplinary environment with a long history of successful investigations into the epidemiology and etiology of childhood respiratory diseases. Data from previous ARSC studies reveal a strong correlation between maternal IgE and Cord blood IgE, and between the mother's cytokine profile (IL-4 and IFNgamma production by stimulated peripheral blood mononuclear cells) and her child's cytokine production at eleven years of age. Maternal IFNgamma production shows an inverse relation to the prevalence of asthma in the child. These correlations were not present between the father and child, suggesting that the mother provides distinct influences in preordaining her child's development of atopy and/or asthma. The placenta has been shown to secrete a number of cytokines which very well could influence differentiation of fetal T cells into either Th1 or Th2 subsets. We hypothesize that atopic women exert an influence on the early immune development of their fetuses/infants though an alteration in the maternal-fetal interface with regard to cytokine production in such a way as to promote fetal/infant T cell differentiation preferentially in a Th2 direction. To test this hypothesis we will address the following specific aims: 1) to elucidate differences in cytokine expression in cord blood mononuclear cells (CBMC) from infants born to atopic as compared to non-atopic mothers and identify any gender-specific sensitivities to maternal effects on early immune development; 2) to characterize the effects of maternal atopy on the decidual cell contributions to the cytokine milieu at the maternal-fetal interface and the relation of this milieu to CBMC function; 3) and to identify differences between atopic and non-atopic women in relation to decidual production of the IL-4 isoforms complete IL-4 and IL4delta2. Our initial studies will focus on identifying differences in cytokine expression in CBMC from infants of atopic versus non-atopic mothers. We will then identify differences in cytokine expression in placental cells and correlate them with differences in CBMC cytokine production. Finally, we will address the issue of IL-4 isoform production by placental cells.
| Brown, Mark; Gustafson, Monica; Saldana, Sandra et al. (2004) Correlation of human decidual and cord blood mononuclear cell cytokine production. Hum Immunol 65:1336-43 |
| Brown, Mark A; Rad, Parmis Y; Halonen, Marilyn J (2003) Method of birth alters interferon-gamma and interleukin-12 production by cord blood mononuclear cells. Pediatr Allergy Immunol 14:106-11 |
