Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We attempted to determine whether various cytokine levels in the serum and synovial fluid (SF) of rheumatoid arthritis (RA) patients are influenced by the performance of filtration leukocytapheresis (LCP). The filtration LCP procedure that used a Cellsorba column (LCP group: n=22; responder subgroup: n=17, non-responder subgroup: n=5) or sham apheresis (control group; n=7) was repeated three times at 1-week intervals. Serum (LCP group, n=22; control group, n=7) and SF (LCP group, n=6; control group, n=3) samples were collected before and after LCP. Levels of tumor necrosis factor alpha (TNFalpha), interleukins (IL-1 beta, IL-2, IL-6, IL-8, IL-10, and IL-15), granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemoattractant protein-1 (MCP-1), RANTES were measured by an enzyme-linked immunosorbent assay. Serum TNF alpha, IL-15, and RANTES were significantly reduced only in the LCP group. Serum IL-10 significantly increased only in the LCP group. In the LCP subgroup, serum IL-15, GM-CSF, and RANTES levels were reduced significantly, while serum IL-10 levels increased significantly only in the responder group after treatment. Serum TNF alpha levels were reduced significantly in both subgroups. Changes in serum IL-10 correlated positively with the improvement of patient's assessment of pain and global severity, and physician's assessment of global severity. These results indicate that the removal of leukocytes from the peripheral blood of RA patients provokes dynamic changes in some cytokine levels in the serum and/or synovial fluid. These changes may explain some of the mechanisms by which the articular symptoms are improved by filtration LCP.
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PMID:Dynamic changes in cytokine levels in serum and synovial fluid following filtration leukocytapheresis therapy in patients with rheumatoid arthritis. 1174 32

1. Mild stress plus mild pain (solvent injection) applied daily to neonatal mice induces hormonal, behavioural and metabolic changes perduring in the adult life. 2. We investigated whether daily mild stress to neonatal mice induces also long-term defined changes of immune response, and whether immune changes are prevented through repeated administration of the opioid antagonist naloxone. 3. Mild stress plus solvent injection administered from birth to the 21st postnatal day causes not only behavioural and metabolic changes, but also long-term (up to 110 days of life) splenocytes modifications, consisting in: increased release of the Th-1 type cytokines interleukin-2 (IL-2) (from an average of 346 to 788 pg ml(-1)), interferon-gamma (from 1770 to 3942) and tumour necrosis factor-alpha (from 760 to 1241); decreased release of the Th-2 type cytokines IL-4 (from 49.1 to 28.4) and IL-10 (from 1508 to 877). Moreover, enhanced natural killer-cell activity; enhanced proliferative splenocytes properties in resting conditions and following phytohemoagglutinin and concanavalin-A stimulation are observed. Immunological, behavioural and metabolic changes are prevented by the opioid antagonist (-)naloxone (1 mg kg(-1) per day s.c., administered instead of solvent) but not by the biologically inactive enantiomorph (+)naloxone. 4. In conclusion, endogenous opioid systems sensitive to naloxone are involved in long-lasting enhancement of the Th-1 type cytokines and cell-mediated immunological response caused by repeated mild stress administered postnatally.
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PMID:Naloxone prevents cell-mediated immune alterations in adult mice following repeated mild stress in the neonatal period. 1187 30

When tissue is destroyed, pain arises. Tissue destruction as well as wound healing are associated with an inflammatory reaction. This leads to activation of nociceptors ("pain receptors") which can cross-communicate with the inflammatory infiltrate. The following review will concentrate on pain-exaggerating (hyperalgesic) and pain-ameliorating (analgesic) mediators which arise from immune cells or the circulation during the inflammation. In the early stages of inflammation endogenous hyperalgesic mediators are produced, including the proinflammatory cytokines IL-1, IL-6 and TNF-alpha, nerve growth factor as well as bradykinin and prostaglandins. Simultaneously, analgesic mechanisms are activated. Opioid peptides such as endorphins, enkephalins and dynorphins are produced by immune cells and can be released locally in the inflamed tissue on stimulation with IL-1 or corticotropin releasing factor. Analgesia is elicited by binding of the opioid peptides to receptors on peripheral sensory neurons. During the course of an inflammatory process, peripheral opioid-mediated analgesia increases. In parallel, antiinflammatory cytokines such as IL-4, IL-10, IL-13 and IL-1ra are produced and reduce hyperalgesic effects of the proinflammatory cytokines initially produced. Inflammatory pain, therefore, is the result of an interplay between hyperalgesic and analgesic mediators. Drugs such as immunosuppressants influencing this interplay may also impair endogenous hyperalgesic and analgesic mechanisms.
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PMID:[Pain and the immune system: friend or foe?]. 1212 5

The antinociceptive effects of interleukin (IL)-4, -10, and -13 were investigated in two different experimental pain models. Our results showed that pretreatment (30 min) with IL-4 (1-5 ng/animal), IL-10 (0.4-10 ng/animal), or IL-13 (0.4-2.5 ng/animal) inhibited the writhing response induced by the i.p. administration of acetic acid (53-89%) or zymosan (63-74%) in mice, and the knee joint incapacitation induced by i.a. injection of zymosan (49-66%) in rats. Neither of the cytokines affected the pain elicited in mice using the hot-plate test. This analgesic effect of IL-4, -10, and -13 was not reversed by the combined pretreatment with the opioid receptor antagonist naloxone. IL-4, -10, or -13 significantly inhibited the release of both tumor necrosis factor (TNF)-alpha (60, 53, and 100%, respectively) and IL-1beta (80, 100, and 100%, respectively) by mice peritoneal macrophages obtained after local (i.p.) injection of zymosan. Antisera against IL-4, -10, and -13 potentiated both the zymosan-induced writhing response and the articular incapacitation. Our results demonstrate that IL-4, -10, and -13 display analgesic activity that is probably not due to endogenous opioid release. This analgesic effect could be related to a peripheral mechanism, probably via the inhibition of the release of the pro-inflammatory cytokines TNF-alpha and IL-1beta by resident peritoneal macrophages.
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PMID:Antinociceptive effects of interleukin-4, -10, and -13 on the writhing response in mice and zymosan-induced knee joint incapacitation in rats. 1249 May 80

Heroin treatment or abusive drug addiction influences many physiological functions, including the reactions of the immune system. Although suppression of various manifestations of the immune system after heroin (or morphine) administration has been reported, we show here that production of proinflammatory cytokines and nitric oxide (NO) was enhanced and allotransplantation reactions were accelerated significantly in heroin-treated recipients. Mice were treated by a subcutaneous administration of heroin (diacetylmorphine) given in one or repeated daily doses. The ability of spleen cells from treated mice to respond in vitro to alloantigens and to produce IL-2, IL-4, IL-10 and IFN-gamma, and the production of IL-1beta, IL-12 and NO by peritoneal macrophages, were tested. Within 2 h after heroin administration, proliferative responses to alloantigens and the production of IL-1beta, IFN-gamma, IL-12 and NO were enhanced significantly. In contrast, the production of anti-inflammatory cytokines IL-4 and IL-10 was at the same time rather decreased. As a consequence, skin allografts in heroin-treated mice were rejected more promptly than in untreated or vehicle-treated recipients. Similarly, the growth of allogeneic tumours induced by high doses of tumour cells was suppressed significantly in heroin-treated mice. The enhancing effects of heroin on the production of proinflammatory cytokines were antagonized by naltrexone, a specific inhibitor of classic opioid receptors. These results show that heroin treatment augments production of proinflammatory cytokines and accelerates allotransplantation reactions. The observations thus illustrate the complexity of the effects of heroin on the immune system and should be taken into account during medical treatment of opiate addicts and in the use of morphine to decrease pain in various clinical situations.
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PMID:Augmented production of proinflammatory cytokines and accelerated allotransplantation reactions in heroin-treated mice. 1265 34

An increase in circulating levels of IL-10 is believed to contribute to immunosuppression caused by major surgery. Cortisol and catecholamines have been shown to be important costimulatory factors for IL-10 secretion in humans. As thoracic epidural block (TEB) should blunt the perioperative increases in cortisol and catecholamines we investigated whether IL-10 secretion is influenced by TEB. Twenty-six patients undergoing coronary artery bypass graft surgery using cardiopulmonary bypass were randomized to receive either general anesthesia (GA) or GA plus TEB. Sensory and pain levels were measured to demonstrate clinical effectiveness. Plasma concentrations of epinephrine, norepinephrine, cortisol, IL-6 and IL-10 as well as monocyte surface expression of HLA-DR and their ex vivo capacity to release TNF-alpha after LPS stimulation were measured perioperatively. TEB was clinically effective and patients receiving TEB showed decreased circulating levels of IL-10. However, this decrease was independent of decreased levels of cortisol or epinephrine. No influence of TEB on IL-6 levels, monocyte capacity to ex vivo release TNF-alpha upon LPS stimulation or their expression of HLA-DR was found. In conclusion, high TEB reduces antiinflammatory immune suppressing mediators including IL-10 and stress mediators. At least in cardiac surgery patients the monocyte functional depression is not related to systemic release of IL-10 and the influence of cortisol or epinephrine is less important for early monocyte deactivation than what in vitro and animal models have suggested.
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PMID:Stress induced IL-10 does not seem to be essential for early monocyte deactivation following cardiac surgery. 1460 65

Central administration of 15 ng interleukin (IL)-1beta in the rat significantly enhanced conditioned fear memory assessed by a passive avoidance task, when retested at 24 and 48 h post-training. Pain threshold was unaffected by 15 ng IL-1beta administration. IL-1beta treatment also increased serum corticosterone. This increase in serum corticosterone was further enhanced in rats given both IL-1beta and footshock. Furthermore, the glucocorticoid receptor antagonist mifepristone blocked IL-1beta-induced elevation in corticosterone and also attenuated the enhanced conditioned fear memory. Central administration of IL-1beta significantly increased prostaglandin E2 and decreased the anti-inflammatory cytokine IL-10 release from whole blood cultures; therefore this treatment appears to be effective in inducing an inflammatory response in both the periphery and the brain. The present study confirms that IL-1beta can enhance conditioned fear memory, an effect which is correlated with changes in glucocorticoid function. This facilitation of defensive behaviour could reflect adaptive responses which may enhance survival during sickness.
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PMID:Interleukin 1 beta enhances conditioned fear memory in rats: possible involvement of glucocorticoids. 1462 8

Systemic syndromes characterized by a persistent activity of circulating mediators (cytokines) are frequently present with advanced cancer. We grouped under the general heading of "Systemic Immune-Metabolic Syndrome (SIMS)" a particular variety of distressing systemic syndrome characterized by dysregulation of the psycho-neuro-immune-endocrine homeostasis, with overlapping clinical manifestations. SIMS may include cachexia, anorexia, nausea, early satiety, fatigue, tumor fever, cognitive changes and superinfection. The aim of this study was to ameliorate some of the SIMS symptoms in a homogeneous group of lung adenocarcinoma patients using a multitargeted therapy. Fifteen patients with evidence of SIMS were studied. SIMS was defined as the presence of weight loss, anorexia, fatigue performance status>/=2 and acute-phase protein response. Patients received medroxyprogesterone (MPA) (500 mg twice daily), celecoxib (200 mg twice daily), plus oral food supplementation for 6 weeks. After treatment, 13 patients either had stable weight (+/- 1%) or had gained weight. There were significant differences in improvement of body-weight-change rate, nausea, early satiety, fatigue, appetite and performance status. Patients who had any kind of lung infection showed higher levels of IL-10 compared to non-infected patients (P=0.039). Our results suggest that patients with advanced lung adenocarcinoma, treated with MPA, celecoxib and dietary intervention, might have considerable improvement in certain SIMS outcomes. This multitargeted symptomatic approach deserves further study.
J Pain Symptom Manage 2004 Jan
PMID:Effects of celecoxib, medroxyprogesterone, and dietary intervention on systemic syndromes in patients with advanced lung adenocarcinoma: a pilot study. 1533 28

Lactoferrin (LF) is a ubiquitous protein which exists in milk, plasma, synovial fluids, cerebrospinal fluid and other biological fluids. LF is also well known as a natural immunomodulator. Recently, we found that bovine milk-derived LF (BLF) produced micro-opioid receptor-mediated analgesia. In this study, we examined whether oral administration of BLF causes anti-nociceptive and anti-inflammatory effects, and also whether it modulates LPS-induced TNF-alpha and IL-10 production in rat model of rheumatoid arthritis (RA), rat adjuvant arthritis. BLF was administrated once daily, starting 3 hr before (preventive experiment) or 19 days after (therapeutic experiment) adjuvant injection. In both experiments, BLF suppressed the development of arthritis and the hyperalgesia in the adjuvant-injected paw. The single-administered BLF produced a dose-dependent analgesia, which was reversed by naloxone, in the adjuvant arthritis rats. Both repeated and single administration of BLF suppressed TNF-alpha production and increased IL-10 production in the LPS-stimulated adjuvant arthritis rats. These results suggest that orally administered BLF has both preventive and therapeutic effects on the development of adjuvant-induced inflammation and pain. Moreover, the immunomodulatory properties of BLF, such as down-regulation of TNF-alpha and up-regulation of IL-10, could be beneficial in the treatment of RA. Thus, we concluded that LF can be safely used as a natural drug for RA patients suffering from joint pain.
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PMID:Oral administration of lactoferrin inhibits inflammation and nociception in rat adjuvant-induced arthritis. 1503 42

Intrathecal (i.t.) catheterization in the rat has been used extensively for drug delivery in various experimental paradigms. These indwelling i.t. catheters have been associated with inflammatory processes and tissue reactions external to the spinal cord in numerous clinical and animal studies. The purpose of this study was to determine whether i.t. catheter placement produced glial activation and changes in specific cytokine expression, i.e. neuroimmune activation, within the spinal cord which might cause altered sensory processing. Rats underwent i.t. catheterization or sham surgery and were killed at 3 or 14 days postsurgery (n> or =3 per group). Spinal cord segments were taken at the cervical level, tip of the catheter and distal to the catheter (thoracic levels). Immunohistochemistry was used to examine spinal localization of the cytokines, interleukin (IL)-6, IL-10 and glial activation (OX-42 for microglia and anti-glial fibrillary acidic protein for astrocytes). At 3 and 14 days after i.t. catheterization, there was an elevation in OX-42 and GFAP expression as compared to control (n=3) and sham surgery (n=4) groups. IL-10-like immunoreactivity was significantly increased in both the dorsal and ventral horns 14 days after i.t. placement as compared to the sham and normal groups. Conversely, IL-6-like immunoreactivity was not significantly different from sham or normal groups. These cytokine findings are discussed in the context of a differential role of specific cytokines in the potential generation of pain states or in the production of analgesia. This study demonstrated that i.t. catheterization induces robust neuroimmune activation that manifests as increases in glial markers and specific cytokine expression. This method should be controlled for, or alternate methods used for, drug delivery in nociceptive animal models that require spinally administered agents.
Eur J Pain 1997
PMID:Intrathecal catheterization alone induces neuroimmune activation in the rat. 1510 97


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