Early eosinophil infiltration into the optic nerve of mice with experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis is a murine model of preclinical autoimmune disease that has pathologic similarities to multiple sclerosis (MS). Although CD4+ T cells have been shown to play a crucial role in the development of disease, we recently demonstrated a link between the development of paralysis and eosinophil infiltration into the spinal cord. As such, CD4+ cells may initiate disease, but eosinophils may be the actual effector cells responsible for causing damage to myelin and causing paralysis. Because MS patients sometimes experience early visual problems, ie, optic neuritis, we explored whether an early eosinophil infiltrate was also observed in the optic nerves of SJL mice after the passive transfer of encephalitogenic T cells. Seven days after the passive transfer of myelin basic protein (MBP)-reactive T cell blasts, we observed a significant infiltration of eosinophils into the optic nerves of the mice. This infiltration persisted during the early phases of paralysis, then declined to baseline values by the peak of limb paralysis on Day 10, and remained at baseline during the remission phase of the disease. Remyelination of optic nerves was observed at this time. These results suggest that eosinophil infiltration into the optic nerve is one of the earliest events occurring after the passive transfer of encephalitogenic T cells in murine experimental allergic encephalomyelitis.

Exercise protects against articular cartilage degeneration in the hamster.

OBJECTIVE: It has been reported that osteoarthritis can occur in hamsters. The present study was undertaken to determine the effects of exercise on the composition of articular cartilage and synovial fluid and on the development of cartilage degeneration in these animals. METHODS: Young (2.5-month-old) group-housed hamsters were compared with 5.5-month-old hamsters that had undergone 3 months of daily wheel running exercise (6-12 km/day) or 3 months of sedentary, individually housed living. The condition of the femoral condyles was determined by scanning electron microscopy in 12 exercising hamsters, 12 sedentary hamsters, and 6 of the young controls. The content of proteoglycan, hyaluronic acid, hydroxyproline, and proline in synovial fluid and patellar cartilage was measured. RESULTS: By scanning electron microscopy, the femoral articular cartilage was smooth and undulating in young controls and older exercising hamsters. In contrast, the femoral condyles were fibrillated in all 12 of the sedentary hamsters. There was no difference in the patellar cartilage collagen content between the 3 groups, but proteoglycan content and synthesis were lower in the patellar cartilage of the sedentary group. Synovial fluid volume was also decreased in the sedentary group compared with the young controls or the older exercising hamsters. CONCLUSION: A sedentary lifestyle in the hamster leads to a lower proteoglycan content in the cartilage and a lower synovial fluid volume. These changes are associated with cartilage fibrillation, pitting, and fissuring. Daily exercise prevents early cartilage degeneration and maintains normal articular cartilage.

Effects of exercise on synovium and cartilage from normal and inflamed knees.

The effect of running activity on normal and inflamed knees was determined by light microscopic (LM) and scanning electron microscopic (SEM) observations on hamster articular cartilage. Animals were split into two groups; one housed in standard cages and one given free access to running wheels. Twenty-one days prior to analysis, half of each group was given an intra-articular injection of lipopolysaccharide (LPS) to cause an inflammation, the other half were uninjected. No remarkable changes were observed by LM in either the control running or nonrunning groups. In contrast, cartilage proteoglycan depletion, and pannus and synovial hyperplasia were equally observed in both groups of LPS-injected animals. SEM observations on the patellae from control animals found them to be free from damage to the articular cartilage. The joints of both the LPS nonrunning and running animals contained synovial hypertrophy with villus projection from the synovial lining. However, only the LPS-injected running hamsters had cartilage fraying over large areas of the articular surface, as well as areas in which the villus projections had been flattened. These results demonstrated that mechanical stress applied to a proteoglycan-depleted cartilage enhances the breakdown of the collagen matrix as judged by fibrillation, and may aggravate the inflammation by crushing the swollen synovial lining where it encroaches on the joint space.

Multiple antigen challenge produces pulmonary eosinophilia but not pulmonary hyperresponsiveness in actively sensitized guinea pigs.

Exposure of actively sensitized boosted guinea pigs to aerosolized antigen, 3 times on alternate days, produced pulmonary eosinophilia but not pulmonary hyperresponsiveness to methacholine Cl measured 3 days after the last antigen challenge. These data suggest that the presence of large numbers of eosinophils in the airways and tissues of the lungs is not sufficient to produce nonspecific pulmonary hyperresponsiveness. These data also suggest that actively sensitized and boosted guinea pigs respond differently to repeated antigen exposure than do asthmatics or wild caught allergic cynomolgus monkeys.