Sex specific aspects in the treatment of inflammation induced gene expression of cytokines by the multi-herbal drug STW 5 in colonic preparations

Sex and gender aspects are important in understanding differences between men and women in their risk and experience of gastrointestinal disorders. Relative to men, women are diagnosed more frequently with irritable bowel syndrome (IBS). It has been discussed that genetic modifications in IL 10 expression could be responsible for the sex differences. The aim of the present study therefore was to determine in gene expression of anti-inflammatory and pro-inflammatory cytokines and to evaluate the effect of the multi-herbal drug STW 5 (Iberogast®) on the gene expression in untreated and inflamed colonic preparations from male and female rats. Comparisons were made with preparations from rats of the same parents. The rats were held in a special room of the animal house to exclude environmental factors. The colonic preparations were pretreated with 2,4,6-trinitrobenzenesulfonic acid (TNBS 10 mM). TNBS induces severe colonic inflammation involving lamina propria mononuclear cells. The gene expression (qRT-PCR) of the proinflammatory cytokines TNF-α and IL 6 as well as the anti-inflammatory cytokine IL 10 was more pronounced in untreated preparations of female rats compared to preparations from male rats. After preincubation with TNBS the gene expression of the cytokines was drastically increased (TNF-α 3.9, IL 6 4.2, IL 10 3.0 fold) in male preparations whereas the increase in female preparation was moderate and ranged from 0.8 (IL 10) to 1.4 (IL 6) fold. STW 5 reduced the TNF-α gene expression and STW 6, a constituent of STW 5, increased the IL 10 gene expression. The detailed sex specific analysis indicated that these effects were only present in preparations of male rats which had low levels of TNF-α and IL 10 genes. Our results clearly indicated sex differences in the cytokine regulation of colonic preparations from male and female animals while an inflammation is induced by TNBS and these could be important for the likewise different action of STW 5 in this model.