Glucocorticoid action on the growth and development of insects

Cortisol increased growth and differentiation in the large milkweed insect (Oncopeltus fasciatus). The glucocorticoid significantly increased the growth of the insect as analyzed by wet and dry weights. Cortisol also stimulated the development of the insects over that of the controls during the six day bioassay.     

Glucocorticoid effects on the production and actions of immune cytokines

The immunosuppressive actions of glucocorticoids form the basis for their use in treatment of autoimmune diseases and prevention of allograft rejection. However, the mechanisms responsible for glucocorticoid-induced immunosuppression are still poorly understood. It is now clear that glucocorticoids do not inhibit all aspects of the immune response and, in some cases, may enhance certain functions of immune effector cells. One example is that of the dramatic increase induced by IFN-gamma in the number of IgG Fc receptors on human mononuclear phagocytes, which is enhanced rather than inhibited by glucocorticoids. An aspect of the immune response which appears to be consistently suppressed by glucocorticoids is the production of immune cytokines. Since these hormones appear to be essential mediators for a vigorous immune response, inhibition of their production may be an effective way for glucocorticoids to block the immune response.     

Glucocorticoid effects on immune cell activation by staphylococcal exotoxins and lipopolysaccharide

Experiments were conducted to determine the effects of physiologically elevated corticosterone on the activation of macrophages and T cells. These studies find that the elevation of corticosterone does not affect the expression of membrane receptors on macrophages and does not affect the activation of macrophages to produce cytokines. In contrast, elevated corticosterone levels correlate with enhanced T cell proliferation to both mitogens and superantigens.     

Glucocorticoid action on connective tissue: from molecular mechanisms to clinical practice

Glucocorticosteroids are highly effective in treating various acute and chronic diseases, but their long-term use is often accompanied by side effects, such as osteoporosis of skeleton and bones and atrophy of the skin. Clinically, many of these side effects involve changes in connective tissue. Glucocorticoid effects on connective tissue metabolism are, however, sometimes beneficial for instance, in the treatment of keloids or autoimmune connective tissue diseases. Recent advances in the biochemical technology have provided tools to examine the molecular mechanisms by which glucocorticoids affect connective tissue. These studies have shown distinct alterations in the extracellular matrix as a result of glucocorticoid treatment. This knowledge is useful for the further development of glucocorticosteroids with desirable action spectrum and with minimal side effects.     

Comments on introducing the immune system

Many attempts to control Complex adaptive systems (CAS) have failed. Here we try to learn from biosystems to derive some principles for CAS management. An application to managing infections is given.     

Comments on introducing the immune system

It is argued that by studying some design principles of the immune system, e.g. nonlinearity and being a complex adaptive system, one can easily find some explanations of basic properties of the system e.g. memory and tolerance.     

Effects of chromium on the immune system

The performance of integral membrane antigens (IMAs) of Mycobacterium habana TMC 5135 in detecting antimycobacterial antibodies in serum and body fluids of patients mainly of extrapulmonary tuberculosis was evaluated. The IMAs were recovered from the detergent phase during Triton X-114 treatment of the plasma membrane of M. habana. Antimycobacterial antibodies were detected by ELISA using IMAs in serum and body fluids of 42 patients and 62 control subjects. As authentic adjunct Mycobacterium tuberculosis antigens were also detected (by ELISA) in body fluids and circulating immune complexes using anti-M. tuberculosis H37Ra antibodies. Anti-M. habana IMA antibody detection increased the positivity rate from 26.% (11/42) and 10% (4/42) obtained by culture and smear microscopy, respectively, to 86% (36/42). M. tuberculosis antigens were also found in 29 out of 36 anti-M. habana IMA antibody-positive cases. Interestingly, all 11 culture-positive cases were also positive for anti-M. habana IMA antibodies. The mean antigen titres in 23 cases, positive for antigens in body fluids, were 2.34 times higher in those who were also positive for anti-IMA antibodies in serum than in those negative for these antibodies. M. habana IMAs may be promising non-tubercular candidate antigens in ELISA-based serodiagnosis of extrapulmonary tuberculosis with substantial sensitivity, specificity and safety.     

Dismantling the immune system

During the past year, we have witnessed a veritable explosion in the number of mutant mouse strains produced by gene targeting in embryonic stem cells. Many of the informative targeted mutants have relevance to the field of immunology. At least one mutant mouse strain now exists for most of the important genes in immunology, and this collection of mutant mice has greatly expanded the experimental repertoire of immunologists. New targeting techniques have been developed that have often found their first application in immunology.     

Effects of opioids on the immune system

Both therapeutic and chronic uses of opioids compromise the optimal functioning of the immune system. Overwhelming evidence suggests that opioid use affects both innate immunity and adaptive immunity. Chronic administration of opioids decreases the proliferative capacity of macrophage progenitor cells and lymphocytes. Additionally, the differentiated function of immune cells is significantly affected by opioids. These effects are mediated by either a direct action of opioids on the target cells or by indirect centrally mediated pathways. Molecular biological and biochemical characterization suggest that immune cells differentially express classical opioid receptors. Interestingly, these studies also reveal the presence of a novel class of opioid receptors in immune cells. We believe that this low affinity morphine binding site mediates the antiproliferative effects of morphine. Special issue dedicated to Dr. Eric J. Simon.     

Glucocorticoid suppression of the sympathetic nervous system and adrenal medulla

Studies were performed to evaluate the effects of glucocorticoids on the activity of the sympathetic nervous system and adrenal medulla. Plasma concentrations of norepinephrine and epinephrine were measured in rats in which endogenous glucocorticoids were removed by bilateral adrenalectomy and in rats to which exogenous glucocorticoids were administered. In intact rats, dexamethasone (2.5, 25 or 250 micrograms) pretreatment suppressed ether vapor-induced elevations of norepinephrine and epinephrine concentrations in plasma. Corticosterone (3 mg/kg), similar to dexamethasone, attenuated the elevation of plasma concentrations of norepinephrine and epinephrine in rats exposed to ether vapor. Glucocorticoids did not alter the elevation of plasma catecholamines stimulated by intracerebroventricular injections of corticotropin-releasing factor or calcitonin gene-related peptide, thus demonstrating functional integrity of the sympathetic nervous system and adrenal medulla. Adrenalectomy resulted in elevation of basal plasma norepinephrine levels and accentuation of ether vapor-induced elevations of plasma norepinephrine concentrations in rats. Dexamethasone (25 ug) administration blunted the effects of adrenalectomy on both basal and ether vapor-stimulated levels of plasma norepinephrine. It is concluded that glucocorticoids acting at as yet undefined sites may be involved in the regulation of sympathetic nervous system and adrenal medullary function.     

Glucocorticoid regulation of the humoral immune system. I. In vivo effects of dexamethasone on IgA and IgG in serum and at mucosal surfaces

The present studies were undertaken to determine whether glucocorticoids influence the levels of Ig in serum, saliva, and vaginal secretions. When measured by RIA, IgA levels in serum were elevated when increasing doses of dexamethasone, a potent synthetic glucocorticoid, were administered to intact- and adrenalectomized-ovariectomized rats. In contrast, IgA levels decreased in saliva and vaginal secretions over the same dose range. Time course studies indicated that the decline in salivary IgA, observed at 24 h after a single injection of dexamethasone, preceded a rise in serum IgA detected at 24 h after the second hormone treatment. Both responses were maximal at day 2 and did not change with further hormone exposure. After immunization and boosting with SRBC at two mucosal sites (intestinal Peyer's patch and uterine lumen), dexamethasone increased anti-SRBC IgA antibody levels in serum and reduced their presence in vaginal secretions. In contrast, anti-SRBC IgG-antibody levels in serum and vaginal secretions were reduced with hormone treatment. In the absence of hormone treatment, pooled sera from nonimmunized animals, when analyzed by HPLC, contained polymeric and dimeric IgA that was present in roughly equal proportion. In response to dexamethasone, polymeric IgA increased to a greater extent than did monomeric IgA. In summary, these studies demonstrate that dexamethasone alters the levels of IgA as well as specifically directed IgA and IgG antibodies in secretions and serum. Further, it suggests that glucocorticoid controlled IgA increases in serum and decreases in vaginal and salivary secretions may be due, in part, to a redistribution of polymeric IgA from mucosal surfaces to serum.     

Glucocorticoid inhibition of estrus in ovariectomized pigs: Relationship to progesterone action

Synthetic glucocorticoids and progesterone were evaluated for their inhibitory action on estrus in ovariectomized pigs treated with estrogen. Triamcinolone acetonide (˜70 μg/kg BW), and dexamethasone (˜140 μg/kg BW) inhibited the estrous response to estradiol benzoate when these glucocorticoids were given during a period of 5 days before to 4 days after estradiol benzoate. The minimum effective dosage of progesterone that would inhibit estrus when given concurrently with estradiol benzoate was 600 (μg/kg BW. When triamcinolone acetonide (30 μg/kg BW) or dexamethasone (125 or 150 μg/kg BW) was given as a single injection in combination with progesterone (100 μg/kg BW), estrous response to estradiol benzoate was again inhibited. These steroids at these dosages had no significant effect when either was administered alone. Based on these results, the inhibitory action of these glucocorticoids on estrus in pigs is additive to the action of progesterone, and we suggest that triamcinolone acetonide and dexamethasone inhibit estrus through mechanisms related to those of progesterone.     

Natural selection on the Drosophila antimicrobial immune system

The evolutionary dynamics of immune defenses have long attracted interest because of the special role the immune system plays in mediating the antagonistic interaction between hosts and pathogens. The antimicrobial immune system of the fruit fly Drosophila melanogaster is genetically well characterized and serves as a valuable model for studying insect and human innate immune defenses. I review here evolutionary and comparative genomic analyses of insect antimicrobial immune genes, with an emphasis on Drosophila. Core signal transduction pathways in the immune system are orthologously conserved across long evolutionary distances, but genes in these pathways evolve rapidly and adaptively at the amino acid sequence level. By contrast, families of genes encoding antimicrobial peptides are remarkably dynamic in genomic duplication and deletion, yet individual genes show little indication of adaptive sequence evolution. Pattern recognition receptors that trigger humoral immunity are evolutionarily rather static, but receptors required for phagocytosis show considerable genomic rearrangement and adaptive sequence divergence. The distinct evolutionary patterns exhibited by these various classes of immune system genes can be logically connected to the functions of the proteins they encode.