Differential Expression of Cytokine mRNA in Skin Specimens from Patients with Erythema Migrans or Acrodermatitis Chronica Atrophicans

Abstract

Erythema migrans, the characteristic skin manifestation of acute Lyme borreliosis, is a self-limited lesion. In contrast, acrodermatitis chronica atrophicans, 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 chronica 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-specific riboprobes. Among the 27 patients who had erythema migrans alone with no associated signs or symptoms, the major cytokines expressed in perivascular infiltrates of T cells and macrophages were the pro-inflammatory cytokine interferon-gamma and the anti-inflammatory cytokine interleukin-10. In the 15 erythema migrans patients who had associated signs and symptoms, including 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 beta, and interleukin-6, were also found. In comparison, infiltrates of T cells and macrophages in the skin lesions of acrodermatitis chronica atrophicans patients had very little or no interferon-gamma expression. Instead, they usually expressed only the pro-inflammatory cytokine tumor necrosis factor alpha and the anti-inflammatory cytokine interleukin-4. Thus, the activation of pro-inflammatory cytokines in erythema migrans lesions, particularly interferon-gamma, seems to be important in the control of the spirochetal infection. In contrast, the restricted pattern of cytokine expression in acrodermatitis chronica atrophicans, including the lack of interferon-gamma, may be less effective in spirochetal killing, resulting in the chronicity of this skin lesion. J Invest Dermatol 115:1115-1123 2000

The emergence of Lyme disease

“…Compared with EM lesions, infiltrates of T cells and macrophages in acrodermatitis lesions had a restricted cytokine profile, lacking IFN-γ production (37). Consistent with this finding, ultraviolet B irradiation of B. burgdorferi-infected C3H mice decreased the Th1 response (69).…”

“…Depending on the Borrelia species and the host, complement-mediated lysis of the organism may be the first line of host defense (Figure 3) (36). On histologic examination, the resulting EM skin lesions consist of mild to marked perivascular infiltrates of lymphocytes, DCs, macrophages, and small numbers of plasma cells (37). As a part of the innate immune response, macrophages engulf and kill spirochetes (38-41).…”

“…Inflammatory cells within the lesion produce primarily proinflammatory cytokines, including TNF-α and IFN-γ (37,42 …”

The Caspase 1 Inflammasome Is Not Required for Control of Murine Lyme Borreliosis

“…In support of this hypothesis, serum levels of IL-1␤ were reported to be elevated in Lyme disease patients, and the levels decreased significantly after doxycycline treatment (35). IL-1␤ mRNA levels in erythema migrans lesions were also shown to be elevated (31).…”

The role of dendritic cells in the pathogenesis of Lyme disease

“…Histological examination of EM is characterized by perivascular influx of lymphocytes, DCs, macrophages and plasmatic cells [27]. The typical feature of EM is a low number of neutrophils, which is quite atypical in …”