Production of colony-stimulating factors and IL-5 by organs from three types of mice with inflammatory disease due to loss of the suppressor of cytokine signaling-1.

Organs from neonatal mice dying from IFN-gamma-dependent inflammatory disease initiated by loss of the gene encoding the suppressor of cytokine signaling-1 (SOCS-1) had a normal capacity to produce G-CSF in vitro but a reduced capacity to produce GM-CSF, most evident with the lung, and some reduction in the production of M-CSF by muscle tissue. In contrast, organs from mice lacking the genes for both SOCS-1 and IFN-gamma had a normal capacity to produce CSFs. Organs from young adult mice dying with polymyositis and myocarditis that lacked SOCS-1 but were heterozygous for IFN-gamma had a normal capacity to produce GM-CSF and M-CSF, but muscle tissue produced significantly increased amounts of G-CSF and IL-5 with IL-5 production also being elevated for the salivary gland, thymus, and heart. Loss of the IFN-gamma gene alone had no impact on organ production of these cytokines in vitro. In none of the inflammatory disease models was IL-3 production detected. The SOCS-1 protein appears to have no direct influence on the cellular production of these cytokines and the abnormalities observed either depend on the coaction of IFN-gamma, or more likely, are linked with the invasion and destruction of tissue by T lymphocytes, macrophages, eosinophils, and neutrophils. The ability of local organs to produce these proinflammatory cytokines could contribute to the development and progression of these inflammatory lesions.