Interleukin-I immunoreactive nerves in heterotopic bone induced by DBM

The occurrence of interleukin-1-positive nerves was investigated by immunchistochemistry in developing heterotopic bone, induced by demineralized allogeneic bone matrix (DBM) in the rat. Interleukin-1 immunoreactivity was observed 1 week after implantation and remained until the end of the experiment at 12 weeks. Immunoreactive material was first identified in mononuclear cells at day 7. Interleukin-1 immunoreactive nerve fibers were first observed in the fibrous tissue at 2 weeks after implantation. A maximum density of fibers was reached at 8 weeks. Abundant immunofluorescent fibers were observed in the marrow tissue of the ossicles, and also in the surrounding fibrous tissue. A substantial number were vascular, but in the bone marrow most of the nerve fibers appeared as irregularly arranged, nonvascular terminals with ramifications and varicosities, intermingled between the marrow cells. No fibers could be detected in the proper bone tissue. The distribution of interleukin-I-positive nerves in the ossicles strongly resembled that previously observed in rat long bones. Moreover, the shape and distribution of the fibers exhibited a striking similarity to that of noradrenergic fibers identified previously both in ossicles and normal rat long bones. The late occurrence and predominant distribution in marrow tissue would seem to imply that neuronal interleukin-1 does not participate in the early differentiation of bone cells. The most important finding seems to be the presence of interleukin-1-positive nerve terminals in blood vessel walls and amidst marrow cells.