Use of granulocyte-macrophage colony-stimulating factor to reverse anergy in otherwise immunologically healthy children

Abstract

T-cell anergy, as measured by delayed hypersensitivity skin testing, is associated with increased susceptibility to infection. Because the repertoire of effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) includes enhancement of antigen processing and presentation by antigen-presenting cells, GM-CSF has been used to augment immune function in human immunodeficiency virus-induced and other viral illness-induced immune dysfunction and to affect positively immune function in a wide variety of disorders. To attempt reversal of T-cell anergy using GM-CSF in 3 otherwise immunologically healthy children with severe recurrent and persistent viral respiratory tract infections and in one child with recurrent bacterial sepsis. After written informed consent and baseline data were obtained, the study participants were administered 3 two-week cycles of GM-CSF. Delayed hypersensitivity skin testing and laboratory tests were repeated 2 weeks after the third cycle and subsequently as clinically indicated. All 4 children developed delayed hypersensitivity by skin testing, and all demonstrated markedly decreased number and severity of infection. Improvement persisted in all patients for at least 1 year. A single cycle of additional treatment in 2 patients reestablished delayed hypersensitivity and decreased infection, both of which persisted throughout the follow-up period of 4 or more years. GM-CSF treatment reversed T-cell anergy in 4 children. Reestablishment of delayed hypersensitivity was associated with a significant decrease in infection. Although further studies will be needed, use of GM-CSF should be considered as an immune modulator in patients with T-cell anergy and recurrent infections.