physiological or infective stress 37 corticotrophin releasing factor crf also has been shown to be a potent inducer of mif expression in cultured pituitary cells a recent functional analysis of the murine mif gene promoter using rat pituitary cells and the pituitary cell line att 20 demonstrated that crf induced gene expression is dependent upon a camp responsive element binding protein 38 interestingly reports of linkage of the crf locus to rheumatoid arthritis have recently appeared in the literature and there is some evidence that the hypothalamic pituitary adrenal hpa axis may play a role in the pathogenesis of rheumatoid arthritis in certain patients patients with active rheumatoid arthritis have been shown to have abnormally low diurnal cortisol levels in the face of normal pituitary and adrenal function suggesting a defect at the hypothalamic level 40 given mif 39 s capacity to counter regulate glucocorticoid action within the immune system reviewed by bucala 1 the expression of mif by the anterior pituitary gland may be important to the development of inflammatory diseases such as rheumatoid arthritis since the initiation of these studies a u2212 173 g c single nucleotide polymorphism snp in the mif gene promoter has been reported by donn et al 41 and was shown to be associated with systemic onset juvenile idiopathic arthritis systemic onset jia the possession of at least one 173 c allele was seen in 36 8 of patients with systemic onset jia compared to 20 3 of the normal population 41 however there is no information concerning the effect of this snp on gene expression a preliminary analysis by the present inventors indicates that the 173 c allele cannot explain the present association data or.