Biologic activity of low dosage IL-2 treatment in vivo. Molecular assessment of cytokine network interaction.

摘要: The sequence of activation the components cytokine network subsequent to in vivo application different dosages IL-2 is still poorly understood. Although side effects therapy are dose dependent, dose-response relationship for induction potentially beneficial or harmful genes remains be studied. We examined patterns gene expression after treatment chronic hepatitis B patients with various doses a phase 1 trial. Total RNAs were isolated from PBMC harvested at time points s.c. injection natural ranging 30,000 1,000,000 U. Dose-dependent on mRNA IL-2, GM-CSF, IFN-gamma, TNF-alpha, and IL-6 assessed using Northern blotting slot techniques. A single U nIL-2 induced selective long-lasting GM-CSF genes, which was not accompanied by accumulation TNF-alpha mRNAs. Larger monokine associated systemic effects. levels cytokines related biologic activity correlated specific proteins cellular parameters: soluble IL-2R serum lymphopenia, neutrophilia, c-reactive protein concentrations. Taken together these data indicate unexpected immunoregulatory activities very low nontoxic vivo.