The invention provides methods and compositions for inhibiting, reducing or slowing inflammation or inflammatory arthritis, for treating inflammatory arthritis such as rheumatoid arthritis, psoriatic arthritis, and a spondyloarthropathy, for inhibiting, reducing or slowing osteoclast differentiation, function, or biological activity, for inhibiting or reducing persistence or accumulation of macrophages at an inflamed site or in an inflamed tissue or for promoting or increasing the efflux of macrophages from an inflamed site or an inflamed tissue, for increasing, stimulating, or promoting lymphocyte cell adhesion, for increasing, stimulating, or promoting lymphocyte efflux from a site of inflammation or from an inflamed tissue, and for decreasing, inhibiting, or reducing a lymphocyte cellular response by inhibiting, inhibiting the biological activity of or antagonizing an axonal guidance protein or a receptor thereof. The axonal guidance protein may be a netrin such as netrin-1, and its receptor may be unc5b.