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

BACKGROUND: 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.
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.