Cytokine mRNA expression in cutaneous warts: induction of interleukin-1 alpha

The persistence of human papillomavirus at cutaneous sites may be due to impaired trafficking of immune effector cells to the epidermis. We investigated whether HPV infection modulates cytokine mRNA expression in skin, thereby influencing local immunity. The mRNA expression of tumour necrosis factor-alpha, interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-1 receptor antagonist (IL-1ra), IL-4, IL-8, IL-10, IL-12, granulocyte macrophage colony-stimulating factor, transforming growth factor-beta, interferon-gamma and amphiregulin were assayed in cutaneous warts and normal skin by semiquantitative reverse transcriptase-polymerase chain reaction. The expression of the cytokines was heterogeneous in the specimens but, of the 12 mRNA species investigated, only IL-10 mRNA was significantly downregulated in warts compared with normal skin (P = 0.002). IL-1 alpha mRNA expression was significantly upregulated in common warts (P = 0.019) and plantar warts (P = 0.003) compared with normal skin. The expression of IL-1 alpha and IL-1ra mRNAs were significantly correlated in plantar warts (P < 0.05). Warts expressing IL-1 alpha also expressed amphiregulin, and there was a significant correlation between the expression of these two genes (P < 0.05). It is possible that IL-1 alpha expression in cutaneous warts may modulate the growth of papillomavirus-infected keratinocytes, mediated by amphiregulin, thus ensuring viral persistence.