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Diet-induced magnesium deficiency in puppies resulted in an increased rate of glucose removal from the blood after intravenous glucose infusions. The levels of immunoassayable insulin in the plasma of these animals were comparable to those of the controls. The accelerated removal of glucose from the plasma was reversed with magnesium treatment. Incubation of intact diaphragms from magnesium-deficient rats demonstrated an increased sugar (2-DG) and amino acid (AIB) uptake from magnesiumfree buffer. Although the plasma magnesium concentration rapidly decreased in the deficient rats, a considerably longer period of time elapsed before the changes in sugar transport became apparent. Kinetic studies suggested that the enhanced permeability was due to carrier mediated transport rather than to diffusion. Tissue magnesium levels remained normal despite a significant decrease in the serum magnesium. These studies suggest that some general characteristic of membrane structure and function is affected by the extracellular concentration of magnesium.

MRL/I mice exhibit many characteristics of human systemic lupus erythematosus including antinuclea r antibodies, circulating immune complexes, glomerulonephritis, and death secondary to renal failure. In addition, these mice have elevated levels of rheumatoid factor and spontaneously develop arthritis that has many similarities to human rheumatoid arthritis. Our present studies indicate that, with age, they also develop reactivity to types I and I1 collagen. The levels of antibodies against native or denatured types I and I1 collagen in the sera of 4-5-month-old MRL/I mice are significantly higher than those in the sera of agematched Balb/c or MRL/n mice. The specificity of these antibodies for collagen was demonstrated by a competitive binding assay. The T cells from 1-or 2-month-old MRL/I mice exhibited a significant proliferative response in the presence of type I collagen and a mild or no response to type I1 collagen. Both antigenic and mitogenic responses decreased with age. The results suggest that the development of autoimmunity to collagen may play an important role in the perpetuation of arthritis, vasculitis, and glomerulonephritis in MRL/I mice. Systemic lupus erythematosus (SLE) is a syndrome with striking diversity of clinical patterns. Among the multiple clinical manifestations, skin lesions, nephritis, arthritis. and pleurisy are commonly observed (1). Several murine models for SLE have been studied and reviewed (2-4). These models have offered a tool for better understanding of the immunologic abnormalities involved in autoimmune diseages. A majority of the studies on murine SLE models have demonstrated a wide range of irregularities in various components of the immune system, including both the B cell and T cell functions.The MRL/l strain of mice exhibits many characteristics of human SLE, such as antinuclear antibodies, circulating immune complexes, glomerulonephritis, and death secondary to renal failure (5,6). The lymphoid hyperplasia, mainly of T cell origin, is also a prominent feature of MRLA mice (7). The cells from enlarged lymph nodes exhibit a reduced concanavalin A (Con Atinduced mitogenic response and interleukin-2 (IL-2) production at 4-6 months of age (8). More recently. Hang et a1 (9) reported that MRL/l mice spontaneously develop an arthritis with many similarities to human rheumatoid arthritis (RA). At about 5 months of age, these mice had a 75% incidence of synovitis. periarticular inflammation, and vasculitis, and in many cases erosion and destruction of articular cartilage by pannus was evident. There was a close relationship between the presence of circulating IgM rheumatoid factor and joint pathology.Another experimental model of arthritis in rats that results from the induction of immunologic reactivity to type I1 collagen, a major component of cartilage, has been described (10). The disease is associated with high levels of cellular and humoral immunity to colla-

Immunization of Lewis rats with native type I1 collagen results in an inflammatory arthritis and increased humoral and cellular immune responses to type I1 collagen. The exposure of rats to native type I1 collagen at day 7 or 10 after immunization suppressed the incidence of arthritis and anticollagen antibody levels, although the cellular response was not affected. The exposure to denatured type I1 collagen offered partial protection, while type I collagen had no significant effect. Rats immunized with Mycobucterium tuberculosis also showed reduced arthritic response when subsequently treated with type I1 collagen. The common modalities between the 2 models and the possible role of type I1 collagen in the interference with the inflammatory arthritic events are discussed.The development of immunity to collagen in various animal species has been described in the literature (1-6). Although immune responses to collagen have been detected in rheumatoid arthritis and other autoimmune diseases in humans (7-1 I), their role in the pathogenesis of these diseases is not completely understood. There has been a renewed interest in this subject since the discovery that immunization of rats and mice of certain strains with native type I1 collagen results in high levels of cell-mediated and humoral immunity, as well as inflammatory arthritis of the joints (12-15).Adjuvant-induced arthritis in rats has been extensively studied as a model for inflammatory joint diseases (16)(17)(18)(19)(20). Some of these reports provide evidence for the immunologic nature of the disease. With an intravenous injection of viable cells from lymph nodes, spleen, or thoracic duct from adjuvant arthritic rats, the disease can be transferred to the syngeneic naive recipients (17,18,20).Trentham et al have demonstrated the cellular sensitivity and detectable levels of circulating antibodies to types I and 11 collagen in adjuvant arthritic rats, as early as 1 week after the onset of arthritis (21). Holoshitz et a1 (22) have demonstrated that a T cell line derived from adjuvant arthritic rats showed a weak proliferative response to type I1 collagen in vitro. Welles and Battisto (23,24) have reported evidence showing that immunization of rats with type I1 collagen, prior to the induction of arthritis with Mycobacterium butyricum, diminished their arthritogenic response (23). Furthermore, immunization of rats with the antibodies to type I1 collagen produced a similar suppression of adjuvant arthritis (24). Recently, Cremer et al (25) have reported that intravenous pretreatment of rats with type I1 collagen does not suppress the incidence or severity of adjuvant arthritis.In the present report, we discuss the effects of intravenous treatments of rats with collagen or Mycobacterium tuberculosis on various inflammatory and immune parameters following induction of type I1 collagen or adjuvant arthritis.

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