Immune activation: the role of pro-inflammatory cytokines in inflammation, illness responses and pathological pain states

It has recently become accepted that the activated immune system communicates to brain via release of pro-inflammatory cytokines. This review examines the possibility that pro-inflammatory cytokines (interleukins and/or tumor necrosis factor) mediate a variety of commonly studied hyperalgesic states. We will first briefly review basic immune responses and inflammation. We will then develop the concept of illness responses and provide evidence for their existence and for the dramatic changes in neural functioning that they cause. Lastly, we will examine the potential roles that both pro-inflammatory cytokines and the neural circuits that they activate may play in the hyperalgesic states produced by irritants, inflammatory agents, and nerve damage. The possibility is raised that apparently diverse hyperalgesic states may converge in the central nervous system and activate similar or identical neural circuitry.     

The role of formalin-induced pain in morphine tolerance, withdrawal, and reward.

The effect of a commonly used experimental pain-induction procedure (formalin injection into a hindpaw site) on morphine tolerance, withdrawal, and reward was examined in rats. Results suggest that the effects of morphine are different in the organism that is experiencing pain at the time it receives the drug than in the organism that is pain free. The presence of pain at the time of each morphine administration decreased analgesic tolerance, decreased naloxone-precipitated withdrawal, and enhanced the rewarding effect of the opiate. These findings, together with those of previous studies, suggest that theories of opiate tolerance, withdrawal, and reward should incorporate the effects of pain. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cognitive mediators in the reduction of pain: The role of expectancy, strategy use, and self-presentation.

Eighty subjects underwent three trials of cold-pressor pain. The first cold-pressor trial served as a baseline. Next, subjects in a neutral (no expectancy information) condition were taught a distraction strategy (shadowing letters) before one cold-pressor trial and an imagery strategy before the other. Subjects in other conditions received positive expectancy information about one of the strategies and negative expectancy information about the other. Negative information reduced expectancy ratings and decreased the magnitude of reported pain reductions. Both pretested levels of social desirability and degree of absorption in strategy use made contributions to the prediction of pain reduction that were independent of expectancy ratings. Theoretical implications are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of prostaglandins in allergic inflammation

Prostaglandins likewise leukotriens are proinflammatory mediators resulting from metabolic degradation of the arachidonic acid originating from membrane phospholipids. The most important products of enzyme cyclooxygenation of arachidonic acid are prostaglandins D2, E2, F2a, tromboxane A2 and prostacyclin. Prostaglandins express their tissue effects via the five basic receptor types. Within the allergic inflammation activated mast cell synthesizes prostaglandin D2 (first lipid mediator) which has bronchoconstrictive and vasodilating effects and attracts neutrophilic leukocytes. Moreover, it also participates in the late phase reactions, six hours subsequent to the exposure to the allergen. This mediator is also important in pathogenesis of urticaria, allergic rhinitis and allergic bronchial asthma. In addition to prostaglandin D2, prostaglandin F2a and tromboxane A2 also have bronchoconstrictive actions, while prostacyclin and prostaglandin E have bronchodilating effects. Inhalation of prostaglandin E prevents asthmatic attacks caused by allergens, strain, metabisulfite and ameliorates attacks of aspirin asthma, which confirms the hypothesis that aspirin asthma is based on cyclooxigenase inhibition and increased leukotriene production. In patients with atopic dermatitis, prostaglandin E has suppressive effects on Interferon gamma production by Th1 helper cells and increases production of Interleukin 4 by the Th2 cells. Tromboxane A2 plays a certain role in the development of bronchial hyperreactivity and late asthmatic response. Prostaglandins are also important mediators in the pathogenesis of allergic conjunctivitis. Most of nonsteroidal antiinflammatory drugs inhibit the enzyme cyclooxygenase and thus also prostaglandin biosynthesis and release.     

The role of thrombocytes in allergic inflammation

Microencephalic rats were obtained through gestational (for the forebrain) or neonatal (for the cerebellum) administration of the DNA-alkylating agent methylazoxymethanol acetate (MAM), which selectively kills dividing cells during neurogenesis. In the microencephalic cerebellum the specific activity of calcium-dependent nitric oxide synthase (NOS) was decreased by 35-40% at 12, 28 and 70 days of age. Other neurochemical markers not related to granule cells (the neuronal population selectively compromised by neonatal MAM treatment), choline acetyltransferase (ChAT) and glutamate decarboxylase (GAD) were not decreased, but actually increased when determined as specific activity. In agreement with the decreased catalytic activity measured in the tube, the expression of neuronal NOS protein was attenuated as judged from immunohistochemistry and Western blotting. In the microencephalic forebrain, the specific calcium-dependent NOS activity measured in homogenates of the whole hemisphere was significantly increased as compared to normal animals. Accordingly, immunohistochemistry for neuronal NOS, as well as NADPH-diaphorase histochemistry revealed an apparent increase in the density of strongly reactive neurons in the underdeveloped cortex and striatum of microencephalic rats. The results reported here demonstrate that permanent alterations of neuronal NOS activity and expression occur when the development of the brain and its neuronal circuits are severely compromised. Furthermore, the permanent downregulation of neuronal NOS in the cerebellum of microencephalic rats may be exploited for the study of the role of NO in mechanisms of synaptic plasticity such as long term depression (LTD).     

The role of cytokines in ocular inflammation

In this paper the immunological mechanisms connected with cytokines in the intraocular inflammation were discussed. The attention was paid to the possible involvement of a cytokine--network in the development of uveitis.     

Interleukin-10: biology, role in inflammation and autoimmunity

LEARNING OBJECTIVES: Reading this article will increase the readers' knowledge of the biology of interleukin-10 (IL-10) an important cytokine. The survival of an organism and its host defense mechanisms require, among other processes, a complex but target-oriented interaction and an interdependence between the immune and inflammatory pathways. The biologic role of interleukin-10 in these processes is presented as well as the possible involvement of IL-10 in the pathogenesis of various diseases. The influence of pharmacologic agents on IL-10 production and the possible pharmacologic role of IL-10 itself are discussed. DATA SOURCES: A detailed literature search was conducted. Studies considered relevant and important involving both humans and animals, in all languages were used. STUDY SELECTION: Material was taken only from peer reviewed journals. RESULTS: IL-10 is produced by CD4+, Tho, Th1, B lymphocytes, mast cells, eosinophils, monocytes, macrophages and keratinocytes. IL-10 has a diverse array of actions, which differ depending on cell type, nature of stimulus and the cellular microenvironment. Interleukin-10 has an important role in the inflammatory and immune systems. In addition, present studies suggest that IL-10 may well play a pivotal role in the pathogenesis of several diseases. It has the potential for therapeutic use. Most of the data on IL-10 have been obtained from in vitro studies or animal experiments. Studies on humans are few, but rapidly increasing. CONCLUSIONS: Interleukin-10 is an important molecule with a central role in maintaining health and in the pathogenesis of disease. Known pharmacologic agents and some under investigation can modify IL-10 production in vivo. Development of agents that can selectively affect a very specific biologic action of IL-10 may provide significant benefit in treating autoimmune and inflammatory diseases.     

The role of eosinophilic leukocytes in allergic inflammation

Eosinophilic leukocytes are tissue cells of granulocytic structure and secretory nature. They are produced in the bone marrow and transported to the targeted tissue via the blood where they are present in concentrations hundred times higher than in peripheral circulation. Eosinophilic leukocytes are the essential effector of allergic inflammation, which is a pathophysiological basis of allergic diseases. These diseases are characterized by disturbed distribution of eosinophilic leukocytes, i.e., peripheral eosinophilia and/or infiltration of the affected organs. Migration of these cells from the peripheral circulation into the targeted tissues, i.e., affected with the allergic inflammation, is influenced by helper T2 cells-dependent cytokines, and other mediators of inflammation. Subsequent to their activation, eosinophilic leukocytes release numerous made and newly produced mediators of inflammation and also present antigens which define their effector function in allergic inflammation. In this way, eosinophilic leukocytes participate in numerous pathological and pathophysiological disorders characteristic of allergic diseases which clearly confirm the active role of these cells in their production.     

The role of inflammation in disk herniation-associated radiculopathy

A series of tripeptide aldehyde derivatives containing variations at the P3 subsite and the amino terminus has been prepared and evaluated for trypsin-like serine protease inhibition. These compounds exhibit strong in vitro inhibition of human plasma kallikrein (HPK), porcine pancreatic kallikrein (PPK) and human plasmin (HP). As suspected from an examination of a related crystal structure, the presence of a hydrophobic residue (adamantyl) at the amino terminus dramatically improves the binding to PPK. The adamantyl group, however, represents a peak in binding; larger residues cause the binding to be reduced, and thus are less well accommodated in this subsite. Although both HP and HPK also can accept large molecular volume at the amino terminus, they do not exhibit the same preference for large residues at this subsite that is demonstrated by PPK. Selectivity differences also are observed with P3 subsite substitution; with PPK preferring a bulky, but compact side-chain (t-butyl) and HP and HPK preferring a more extended (e.g. benzyl) group.     

"The role of the family in the development of psychopathology": Erratum.

Reports an error in the original article by G. H. Frank (Psychological Bulletin, 1965, Vol 64[3], 191-205). The eighth item in the bibliography should have been attributed to Garmezy, Farina, and Rodnick (1960) rather than Bell, Garmezy, Farina, and Rodnick. The author also stated incorrectly that the parents' responses to the PARI were used as the content of the interaction between parents in the studies reported in Farina (I960), Farina and Dunham (1963), and Garmezy, Farina, and Rodnick (1960); it was, rather, sets of hypothetical situations adapted from a research method used by Jackson (1956). As was indicated in Frank's presentation, the common denominator in these particular research endeavors was that they were predicated on the basic model established by Strodtbeck (1951), that is, eliciting the attitudes of parents by having them respond to written material with their opinions, individually, then in interaction with each other; the error was in recording what constituted the material by which the parental attitudes were elicited.. (The following abstract of this article originally appeared in record 1965-15947-001.) Psychologists generally make the assumption that the experiences to which the individual is exposed over a period of time lead to the development of learned patterns of behavior. From this, psychologists have reasoned that the experiences the individual has in his early life at home, with his family, in general, and his mother, in particular, are major determinants in the learning of the constellation of behaviors subsumed under the rubric, personality, and in particular, the development of psychopathology. A review of the research of the past 40 yrs failed to support this assumption. No factors were found in the parent-child interaction of schizophrenics, neurotics, or those with behavior disorders which could be identified as unique to them or which could distinguish one group from the other, or any of the groups from the families of the controls. (PsycINFO Database Record (c) 2010 APA, all rights reserved)