Differential expression of cytokine mRNA in skin specimens from patients with erythema migrans or acrodermatitis chronica atrophicans

Erythema migrans, the characteristic skin manifestation of acute Lyme borre liosis, is a self-limited lesion. In contrast, acrodermatitis chronica atro phicans, the typical cutaneous manifestation of late Lyme borreliosis, is a chronic skin condition. In an effort to understand pathogenic factors that lead to different outcomes in dermatoborrelioses, skin biopsy samples from 42 patients with erythema migrans and 27 patients with acrodermatitis chro nica atrophicans were analyzed for mRNA expression of five pro-inflammatory cytokines (tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, interferon-gamma, and interleukin-2) and two anti-inflammatory cytokines ( interleukin-4 and interleukin-10) by in situ hybridization with cytokine-sp ecific riboprobes. Among the 27 patients who had erythema migrans alone wit h no associated signs or symptoms, the major cytokines expressed in perivas cular infiltrates of T cells and macrophages were the pro-inflammatory cyto kine interferon-gamma and the anti-inflammatory cytokine interleukin-10. In the 15 erythema migrans patients who had associated signs and symptoms, in cluding headache, elevated temperature, arthralgias, myalgias, or fatigue, a larger number of macrophages and greater expression of macrophage-derived pro-inflammatory cytokines, tumor necrosis factor alpha, interleukin-1 bet a, and interleukin-6, were also found. In comparison, infiltrates of T cell s and macrophages in the skin lesions of acrodermatitis chronica atrophican s patients had very little or no interferon-gamma expression. Instead, they usually expressed only the pro-inflammatory cytokine tumor necrosis factor a and the anti-inflammatory cytokine interleukin-4. Thus, the activation o f pro-inflammatory cytokines in erythema migrans lesions, particularly inte rferon-gamma, seems to be important in the control of the spirochetal infec tion. In contrast, the restricted pattern of cytokine expression in acroder matitis chronica atrophicans, including the lack of interferon-gamma, may b e less effective in spirochetal killing, resulting in the chronicity of thi s skin lesion.