IL-17, neutrophil activation and muscle damage following endurance exercise.

The T-cell subset Th17 is induced partly by interleukin (IL)-6 and activated by IL-23, and produces a proinflammatory cytokine IL-17. Since IL-6 increases dramatically following long-lasting endurance exercise, this response may also stimulate the induction of IL-17 and IL-23 after exercise. The aim of this study was to clarify the dynamics of IL-17 in association with endurance exercise-induced muscle damage and inflammatory responses. Fourteen male triathletes participated in a duathlon race consisting of 5 km of running, 40 km of cycling and 5 km of running. Venous blood and urine samples were collected before, immediately after 1.5 h and 3 h after the race. Plasma and urine were analyzed using enzyme-linked immunosorbent assays (ELISA). Haematological and biochemical variables such as neutrophil activation marker (myeloperoxidase: MPO), muscle damage marker (myoglobin: Mb) and soluble receptor activator of nuclear factor (NF)-KB ligand (sRANKL) were also determined to estimate the biological and pathological significance. Plasma concentrations oflL-6 (+26.0x), MPO (+3.2x) and Mb (+4.9x) increased significantly immediately after the race and IL-17 and IL-23 tended to increase. Furthermore, plasma concentrations of IL-12p40 and sRANKL increased significantly after the race. The measured parameters related to Thl 7 cytokines in the urinary output were closely correlated with each other and muscle damage marker. These findings suggest that IL-17 induced by IL-6 and activated by IL-23 or other IL-17 producing-cells and IL-23 might promote neutrophil activation and muscle damage following prolonged endurance exercise.

Hypogammaglobulinemia in McArdle myopathy (glycogenosis type V).

Glycogenosis type V (McArdle) was the first myopathy to be enzymatically defined myopathy and has been found in approximately 120 patients. It is characterized by a myophosphorylase defect. In 2 patients with completely missing phosphorylase activity, muscle fiber necrosis and creatinine kinase elevation, we found reproducibly low gammaglobulins and low immunoglobulin-G. Compared with 124 nonmyopathic control patients with hypogammaglobulinemia, we did not find any established cause for low gammaglobulins in either case of McArdle disease. Myopathies with selected laboratory features or histopathology in common did not show changes in gammaglobulins or immunoglobulins. Unaffected family members had normal gamma-globulins and immunoglobulins. Therefore, gammaglobulins indicate an immunologic involvement in phosphorylase deficiency, and a potential for genomic co-localization.

Lactate dehydrogenase M-subunit deficiency: a new type of hereditary exertional myopathy.

Three families with a complete deficiency of the lactate dehydrogenase M subunit show exertional myoglobinuria. The response to ischemic forearm work is characteristic in these three families: an increase of venous lactate concentration after ischemic work was not observed and a marked increase of venous pyruvate was found. Glycolysis was markedly retarded in the patient's muscle in the glyceraldehyde 3-phosphate dehydrogenase (GA3PD) step. A significant increases in glyceraldehyde 3-phosphate, dihydroxyacetone phosphate and fructose 1,6-diphosphate were observed. The glycolysis retardation may be attributed to the impaired reoxidation of NADH produced by GA3PD action. The cytosolic fraction of skeletal muscle is rich in alpha-glycerophosphate dehydrogenase. This enzyme reoxidizes the excess NADH and drains triose phosphates from the glycolytic pathway under anaerobic conditions. For this reason, ATP production was significantly impaired and muscle cells were damaged in these patients. Consequently, the cytosolic enzymes and proteins such as creatine kinase and myoglobin were released into the blood stream. Otherwise, patients with a lactate dehydrogenase M-subunit deficiency do not show muscle stiffness and myoglobinuria under ordinary circumstances. They complain of muscle rigidity and sudden myoglobinuria after strenous exercise under anaerobic conditions. Thus, the lactate dehydrogenase M-subunit deficiency does not show any symptoms under ordinary circumstances, but is a latent hereditary disorder, now recognized as a new type of hereditary exertional myoglobinuria.

Active and passive immunization to angiotensin in experimental acute renal failure.

A number of studies support, and others fail to support, the concept that the renin-angiotensin system plays a key role in the pathogenesis of acute renal failure. This study, employing active and passive immunization against angiotensin II, was designed to examine the primacy of circulating angiotensin as a mediator of this syndrome. Neither mode of immunization significantly affected the degree of azotemia or the marked reduction of inulin clearance expected in rats subjected to glycerol-induced myohemoglobinuria. Twenty-four hours after challenge, inulin clearance (Cin) in actively immunized rats fell to 3.2% of control and that of unimmunized rats given the same dose of glycerol was 2.5% of control. Although there was some variation among groups of passively immunized rats, Cin of one group being 18% of control, Cin of the other groups was less than 3% of control. The dose and binding capacity of the immune globulin used here were essentially the same as those reported in another study in which immunization was thought to be of prophylactic value in rats subjected to s.c. administered glycerol injections. Technologic differences unrelated to immunization are suggested to have caused the difference in results in the two studies, and it seems doubtful that circulating angiotensin plays a key role in the pathogenesis of myohemoglobinuric acute renal failure in the rat.