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Cytokine Sep 2022Cellular communication mediated by cytokines is an important mechanism dictating immune responses, their cross talk and final immune output. Cytokines play a major role... (Review)
Review
Cellular communication mediated by cytokines is an important mechanism dictating immune responses, their cross talk and final immune output. Cytokines play a major role in dictating the immune outcome to cancer by regulating the events of development, differentiation and activation of innate immune cells. Cytokines are pleiotropic in nature, hence understanding their role individually or as member of network cytokines is critical to delineate their role in tumour immunity. Tumour systemically manipulates the immune system to evade and escape immune recognition for their uncontrollable growth and metastasis. The developing tumour comprise a large and diverse set of myeloid cells which are vulnerable to manipulation by the tumour-microenvironment. The innate immune cells of the monocytic lineage skew the fate of the adaptive immune cells and thus dictating cancer elimination or progression. Targeting cells at tumour cite is preposterous owing to their tight network, poor reach and abundance of immunosuppressive mechanisms. Monocytic lineage-derived cytokines (monokines) play crucial role in tumour regression or progression by either directly killing the tumour cells with TNFα or promoting its growth by TGFβ. In addition, the monokines like IL-12, IL-1β, IL-6, IL-10 and TGFβ direct the adaptive immune cells to secrete anti-tumour cytokines, TNFα, IFNγ, perforin and granzyme or pro-tumour cytokines, IL-10 and TGFβ. In this review, we elucidate the roles of monokines in dictating the fate of tumour by regulating responses at various stages of generation, differentiation and activation of immune cells along with the extensive cross talk. We have attempted to delineate the synergy and antagonism of major monokines among themselves or with tumour-derived or adaptive immune cytokines. The review provides an update on the possibilities of placing monokines to potential practical use as cytokine therapy against cancer.
Topics: Cytokines; Humans; Interleukin-10; Monocytes; Monokines; Neoplasms; Transforming Growth Factor beta; Tumor Microenvironment; Tumor Necrosis Factor-alpha
PubMed: 35764025
DOI: 10.1016/j.cyto.2022.155948 -
Poultry Science Aug 1991Stimulation of the immune system results in a series of metabolic changes that are antagonistic toward growth. Monokines, including interleukin-1, tumor necrosis factor,... (Review)
Review
Stimulation of the immune system results in a series of metabolic changes that are antagonistic toward growth. Monokines, including interleukin-1, tumor necrosis factor, and interleukin-6, are released from cells of the monocyte-macrophage lineage after recognition of immunogens. They appear to mediate homeorhetic response, which alters the partitioning of dietary nutrients away from growth and skeletal muscle accretion in favor of metabolic processes which support the immune response and disease resistance. These alterations include 1) decreased skeletal muscle accretion due to increased rates of protein degradation and decreased protein synthesis; 2) increased basal metabolic rate resulting in increased energy utilization; 3) use of dietary amino acids for gluconeogenesis and as an energy source instead of for muscle protein accretion; 4) synthesis by the liver of acute phase proteins; 5) redistribution of iron, zinc, and copper within the body due to the hepatic synthesis of metallothionein, ferritin, and ceruloplasmin; (6) impaired accretion of cartilage and bone; and 7) release of hormones such as insulin, glucagon, and corticosterone. These monokines also influence the differentiation of cells. Tumor necrosis factor suppresses the differentiation of myoblasts and adipocytes whereas the chicken monokine myelomonocytic growth factor induces the differentiation of granulocytes.
Topics: Acute-Phase Proteins; Animals; Body Composition; Bone and Bones; Eating; Endocrine Glands; Energy Metabolism; Humans; Lipid Metabolism; Liver; Monokines; Muscle Development; Poultry
PubMed: 1717968
DOI: 10.3382/ps.0701781 -
Beitrage Zu Infusionstherapie Und... 1987
Review
Topics: Biological Products; Humans; Interferon-gamma; Interleukins; Lymphokines; Macrophage Activation; Monokines; Tumor Necrosis Factor-alpha
PubMed: 3125828
DOI: No ID Found -
Federation Proceedings Feb 1985The role of the macrophage system in shock pathogenesis now embraces both classic endocytic functions as well as the more recently discovered function of the macrophages... (Review)
Review
The role of the macrophage system in shock pathogenesis now embraces both classic endocytic functions as well as the more recently discovered function of the macrophages as a multifaceted secretory apparatus. Among the major macrophage secretory products are the monokines, regulatory proteins that mediate via both local or paracrine and systemic or endocrine mechanisms, the nonspecific host defense and metabolic responses to inflammation and sepsis. Evidence is reviewed for a monokine involvement in the alterations of protein, fat, and carbohydrate metabolism in sepsis and/or endotoxicosis, viz., enhanced muscle proteolysis, enhanced hepatic acute phase protein synthesis, depressed lipogenesis and lipoprotein lipase function, enhanced peripheral glucose oxidation, and depression of hepatic gluconeogenesis. Monokines are also related to the disturbed endocrine mechanisms of sepsis, viz., enhanced insulin secretion and depressed adrenal steroidogenesis. It is suggested that the macrophage system mediates via secretion of monokines an integrated fuel substrate and hormonal adjustment to sepsis, which on the one hand may provide optimal metabolic homeostasis for systemic host defense, but on the other hand, if allowed to act unchecked, may contribute to the metabolic dyshomeostasis of septic shock.
Topics: Animals; Carbohydrate Metabolism; Homeostasis; Hormones; Humans; Lipid Metabolism; Macrophages; Monocytes; Monokines; Proteins; Shock, Septic
PubMed: 3881289
DOI: No ID Found -
The Year in Immunology 1989
Review
Topics: Animals; Biological Factors; Brain; Humans; Hypothalamo-Hypophyseal System; Interleukin-1; Lymphokines; Monokines; Neuroimmunomodulation; Pituitary-Adrenal System
PubMed: 2652928
DOI: No ID Found -
Nihon Rinsho. Japanese Journal of... May 1987
Review
Topics: Amino Acid Sequence; Animals; Humans; Interleukin-1; Leukocytes; Macrophages
PubMed: 3306020
DOI: No ID Found -
Advances in Experimental Medicine and... 1990It has long been known that endogenous pyrogen, released as a result of injection of typhoid vaccine or in response to infection, produces fever and increases ACTH... (Review)
Review
It has long been known that endogenous pyrogen, released as a result of injection of typhoid vaccine or in response to infection, produces fever and increases ACTH secretion. Recent studies have indicated that endogenous pyrogen is, at least in part, IL-1. This monokine has now been shown to activate the release of ACTH by a hypothalamic mechanism with release of CRF and possibly vasopressin, which stimulates the corticotrophs. There may also be a pituitary action to stimulate the release of ACTH directly. In our experiments we showed that IL-1 at low but not higher doses appears to act intrahypothalamically to stimulate GH and PRL release and to inhibit TSH release. In the meantime, another monokine, cachectin, was isolated and its structure determined. We have found that this monokine can act following its third ventricular injection to stimulate ACTH, PRL, and GH release and to inhibit TSH release, at least in part, by release of prostaglandins since indomethacin, an inhibitor of prostaglandin synthesis, produced a blockade of the responses except for those of ACTH. This peptide also has highly potent effects to alter pituitary hormone release by direct action on the pituitary to stimulate ACTH, GH, and TSH and to a slight extent PRL release. These actions appear to involve prostaglandins since indomethacin blocks all of the effects except for the effect on ACTH secretion. This monokine also produces a dose-related lowering of anterior pituitary cyclic AMP levels. When the monokine was incubated along with somatostatin, the lowering of cyclic AMP was reversed, and a potent PRL-releasing effect of the monokine was visible. We have begun studies with a third monokine, gamma interferon, which indicate that it stimulates ACTH release but suppresses plasma GH and TSH levels by a hypothalamic action. It is apparent that these various monokines have powerful effects to alter hypothalamic-pituitary function and that they probably mediate most of the effects of infections on the release of anterior pituitary hormones.
Topics: Animals; Humans; Monokines; Pituitary Hormones, Anterior
PubMed: 2239430
DOI: 10.1007/978-1-4684-5799-5_20 -
Progress in Clinical and Biological... 1989Multiple organ failure continues to be the primary cause of death after trauma and sepsis. This clinical syndrome represents the transition from a hypermetabolic... (Review)
Review
Multiple organ failure continues to be the primary cause of death after trauma and sepsis. This clinical syndrome represents the transition from a hypermetabolic response to injury to a syndrome of progressive organ failures and death. Risk factors include: perfusion deficits, persistent foci of dead or injured tissue, an uncontrolled focus of infection, the presence of the respiratory distress syndrome, persistent hypermetabolism, and preexisting fibrotic liver disease. Once initiated, most treatment modalities for the organ failure syndrome become progressively ineffective including: ventilation, antibiotics, nutrition, and surgery. The best treatment remains prevention and rapid control of risk factors including restoration of oxygen transport and aggressive nutrition support. There seems to be no treatment "magic bullet" either experimentally or clinically once the syndrome has occurred. The metabolic response to injury involves alterations in physiology and in the metabolism of carbohydrate, fat and amino acids. These changes seem to reflect the modulation of the end-organs by the mediator systems activated in response to the stress stimuli. The transition from hypermetabolism to organ failure appears to reflect the clinical appearance of liver failure. It is hypothesized that this liver failure may represent a state of regulatory dysfunction induced in large part by the activated hepatic macrophage, the Kupffer cell. The activation of these macrophages is hypothesized to represent the final stage of a series of stimulating events, eg. hypoxia, endotoxin, bacteria, and gut translocated toxins. The precise monokine(s) responsible are not yet completely characterized, although Interleukin-1 (IL-1) and tumor necrosis factor (TNF) appear to be involved as do prostaglandins (Pg) such as PgE2.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Animals; Biological Factors; Humans; Liver; Macrophage Activation; Monokines; Multiple Organ Failure; Shock, Septic
PubMed: 2648413
DOI: No ID Found -
Science (New York, N.Y.) Nov 1985Hepatocyte-stimulating factor and interleukin-1 are proteins produced by monocytes in response to inflammatory challenge. Neither of these monokines had direct effects...
Hepatocyte-stimulating factor and interleukin-1 are proteins produced by monocytes in response to inflammatory challenge. Neither of these monokines had direct effects on steroid production by cultured adrenocortical cells. Both monokines stimulated pituitary cells (AtT-20) to release adrenocorticotropic hormone; interleukin-1 was equipotent with a combination of corticotropin-releasing factor and arginine vasopressin, and hepatocyte-stimulating factor was at least three times as effective. The synthetic glucocorticoid, dexamethasone, inhibited production of hepatocyte-stimulating factor by cultured monocytes. These results indicate an axis between monocytes and pituitary and adrenocortical cells which may play a role in regulating host defense.
Topics: Adrenal Glands; Adrenocorticotropic Hormone; Animals; Interleukin-1; Interleukin-6; Mice; Monocytes; Monokines; Pituitary-Adrenal System; Proteins; Secretory Rate
PubMed: 2997929
DOI: 10.1126/science.2997929 -
Digestive Diseases and Sciences Mar 1988IL-1 is a polypeptide product of various cells that mediates several components of the acute-phase response to infection and injury. Its most dramatic biological... (Review)
Review
IL-1 is a polypeptide product of various cells that mediates several components of the acute-phase response to infection and injury. Its most dramatic biological property is its ability to induce arachidonate metabolites in a variety of cells including PGE in the brain, fibroblasts, synovial cells, and chondrocytes; in addition, IL-1 induces lipoxygenase products in lymphocytes and other cells. IL-1 has been cloned. There are two forms. The predominant form of IL-1 from human monocytes has a pI of 7 (also called beta) and is initially synthesized as a precursor molecule (31 kD). A minor form (less than 100-fold) also exists (pI 5, also called alpha). IL-1 seems unique among the lymphokines and monokines in that there is no signal peptide sequence for cleavage. Depending on the stimulus, intracellular levels of precursor IL-1 can be high, whereas some cell activators result in large amounts of processed IL-1. Precursor IL-1 is cleaved into a 17.5-kD peptide, which is the predominant extracellular form. IL-1 induces prostaglandins and lymphocyte activation as well as many different biological activities. These include fever, PGE production, protease release from synovial cells and chondrocytes, bone resorption, acute-phase protein synthesis, and other effects. Although there are few studies showing an IL-1 effect on the gastrointestinal tract, the multiple biological properties of IL-1 suggest that IL-1 plays a role in inflammatory bowel disease as well as in mediating some of the gastrointestinal changes observed in systemic acute-phase responses.
Topics: Acute-Phase Reaction; Animals; Colitis, Ulcerative; Crohn Disease; Humans; Inflammation; Interleukin-1; Recombinant Proteins; Tumor Necrosis Factor-alpha
PubMed: 3126028
DOI: 10.1007/BF01538128