The invention provides methods and compositions for inhibiting, reducing or slowing inflammation or inflammatory diseases, for reducing sequestration or collecting or localization of macrophages, for treating a disease caused all or in part by or characterized by inflammation such as, for instance, chronic inflammation, for inhibiting, slowing, reversing or preventing atherosclerosis, and for increasing insulin sensitivity, decreasing or inhibiting resistance to insulin, or treating diabetes by inhibiting, inhibiting the biological activity of or antagonizing an axonal guidance protein. The methods may feature administering to a subject a therapeutically effective amount of an agent effective to inhibit or reduce the biological activity of an axonal guidance protein or a receptor of the axonal guidance protein, or an analog, derivative or combination thereof. The disease may be, for instance, one of atherosclerosis, rheumatoid arthritis, tuberculosis, autoimmune syndromes and obesity where macrophage accumulation in adipose tissue is known to promote insulin resistance.
