Human ciliary neurotrophic factor (human CNTF) mutants, in which at least the amino acid residue corresponding to position 153 of wild type human CNTF has been substituted with another amino acid residue in the amino acid sequence encoding human CNTF, exhibit an activity comparable or superior to that of wild type human CNTF. It is therefore expected that the human CNTF mutants would be effective as drugs with improved side effects such as reduction in appearance of an autoantibody, loss of body weight, anorexia, a dry cough, fatigue, etc.In cytokines having sequence similarity to human CNTF and abundant .alpha. helices (GH, PRL, EPO, G- CSF, LIF, IL-6, IL-2, IL-4, GM-CSF), there are further provided mutants in the D1 cap region.