The innate immune system in delayed cutaneous allergic reactions to medications

Innate immune responses are attracting increasing interest from researchers in the field of drug allergy. This review discusses recent advances in the understanding of several innate immune components in delayed cutaneous hypersensitivity reactions to medications, with special attention on severe reactions.

The mechanism of activation of dendritic cells in response to drugs is being unravelled. Activated monocytes and macrophages have been found in affected skin of bullous diseases. Increased gene expression of monomyeloid cell products including several 'alarmins' or endogenous damage-associated molecular patterns has been described in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Natural killer (NK) cells from patients respond to drugs in vitro. In-vivo, NK cells may contribute to severe diseases through the secretion of effector molecules such as granulysin. The innate receptor CD94/NKG2C is expressed by NK cells and cytotoxic T lymphocytes in SJS/TEN and triggers degranulation in response to human leukocyte antigen-E-expressing keratinocytes. T cells with innate activities have been detected in patients during severe acute reactions.

Humoral and cellular components of the innate immune response have been identified in association with delayed drug hypersensitivity reactions. Their participation in certain diseases may explain the variability of phenotypes in hypersensitivity reactions to medications.