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)

Emergent or elective surgical procedures may be complicated by sepsis, resulting in critical illness that can lead to organ failure and death. The opioid drug, morphine is widely used to alleviate pain in post-surgical patients; however, it is well documented that chronic treatment of mice with morphine affects the proliferation, differentiation and function of immune cells. Thus, morphine might be expected to exacerbate the effects of sepsis, which also compromises the immune system. To test this notion, we investigated the effect on several immune functions of a clinical dose of morphine (4 mg/kg) superimposed upon a lipopolysaccharide (LPS)-induced infection model. Our results show that this relatively low dose of morphine, though generally having no effects on immune parameters by itself, significantly augmented LPS responses. A clinical dose of morphine (4 mg/kg body weight) superimposed upon an animal model of sepsis resulted in a significant increase in mortality at 48 h. In the absence of the drug, most septic animals died after 96 h. Phenotypic responses such as, decreased thymic cellularity, compromised mitogenic response and inhibition of IL-2 synthesis that are evident at 48-72 h after LPS injection appear as early as 24 h in animals that receive morphine in addition to LPS. In addition, our results show that in T cells there is a shift from TH1 type cytokine elaboration to a TH2 type cytokine elaboration in animals that receive both LPS and morphine.
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PMID:Morphine synergizes with lipopolysaccharide in a chronic endotoxemia model. 1022 20

Adrenal medullary tissue including chromaffin cells was grafted intrathecally in cancer patients to relieve intractable pain. The central nervous system (CNS) is considered an immune privileged site. Therefore, non-HLA-matched and unencapsulated tissue was grafted in 15 patients and 1 sham control in a series of at least 20 grafts. We observed an increase in CSF lymphocyte counts in 15/20 allografts (75%). In contrast to peripheral blood, CD4 T cells predominated in the CSF, but failed to exhibit an activated phenotype (CD25+ CD45RO+ HLA-DR+). The positive effect of graft on pain, the high met-enkephalin levels, the absence of any increase in CSF cytokine levels particularly for IFN-gamma or IL-2 (but not IL-10 and IL-6), indirectly indicated that the graft was tolerated despite the presence of CSF lymphocytes. The single treatment failure and three of four cases of partial efficacy occurred in grafts where CSF lymphocytes were present. Moreover, when assayed (n = 7), the CD4+ CSF lymphocytes still retained the capacity to exhibit ex vivo a normal or enhanced frequency of T CD4 cells producing IFN-gamma and IL-2. Taken together, our observations indicate that impairment of the local immunosuppressive balance can lead to activation of those CSF CD4 T cells and drive a rejection process. This study suggests further work on the purification and/or the immunoisolation of tissues grafted in the CNS will be necessary, particularly when the possibility of long-term and repeated grafting is considered.
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PMID:Intrathecal grafting of unencapsulated adrenal medullary tissue can bring CD4 T lymphocytes into CSF: a potentially deleterious event for the graft. 1078 70

IL-2 immunotherapy has been proven to be effective in the treatment of metastatic renal cell cancer (RCC). However, several drugs commonly used in the palliative therapy of cancer may potentially influence IL-2 efficacy, since the anticancer immunity has appeared to depend on complex interactions between immune system and psychoneuroimmunomodulation. In particular, experimental studies and preliminary clinical investigations have shown that the opioid substances, namely morphine, may suppress the anticancer immunity and the efficacy of IL-2 itself. In contrast, other neuroactive substances, in particular the pineal hormone melatonin (MLT), have been proven to stimulate the immune response, including the anticancer immunity, and to abrogate opioid-induced immunosuppression. On this basis, a study was planned to evaluate the effect of a concomitant MLT administration on the efficacy of IL-2 immunotherapy in advanced cancer patients chronically treated with morphine for cancer-related pain. The study was carried out in 30 metastatic RCC patients under chronic therapy with morphine at oral doses ranging from 60 to 120 mg/day. Patients were randomized to receive morphine alone or morphine plus MLT (20 mg/day orally in the evening). The immunotherapeutic cycle consisted of IL-2 subcutaneous administration at a dose of 6 million IU/day for 6 days/week for 4 consecutive weeks. In nonprogressing patients, a second cycle was planned after a 21-day rest period. The percent of partial responses achieved in patients treated with morphine alone was significantly lower than that observed in patients concomitantly treated with MLT (1/16 vs. 4/14, p<0.05). Moreover, the 3-year percent of survival was significantly higher in patients concomitantly treated with MLT (p<0.01). In contrast, no diminished analgesic efficacy of morphine occurred in patients concomitantly treated with MLT. This preliminary study seems to suggest that the negative influence of morphine therapy for cancer-related pain on the clinical efficacy of IL-2 cancer immunotherapy may be abrogated by the concomitant administration of the immunomodulating pineal neurohormone MLT.
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PMID:Abrogation of the negative influence of opioids on IL-2 immunotherapy of renal cell cancer by melatonin. 1085 53

The present study was designed to investigate the involvement of mu receptor in interleukin 2-induced antinociception. Intraplantar injection of human recombinant interleukin 2 (rIL-2) (1. 5x10(4) U) significantly enhanced pain threshold as measured by paw withdrawal latencies (PWLs) to noxious radiant heat in normal rats. After administration of rIL-2, PWLs were also markedly increased in morphine-tolerant and chronic constriction injury (CCI)-operated rats, which have been proven morphine-insensitive. rIL-2-induced antinociception in both morphine-tolerant and CCI-operated rats was significantly lower than that in normal rats. rIL-2 antinociception was partially blocked by naloxone (1 mg/kg i.p.) in normal rats but remained unchanged in the CCI group. Our results suggest that the use of rIL-2 in human medical practice may be extended for its effectiveness in relief of neuropathic pain induced by CCI. Here we infer that mu receptor plays an critical role in IL-2-induced antinociception and that there are also some other receptors involved in this process.
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PMID:Interleukin 2-induced antinociception partially coupled with mu receptor. 1093 Mar 4

Spaceflight alters many immune responses and among the regulatory components of an organisms response system that have been to be affected by spaceflight is the cytokine network. Spaceflight, as well as ground-based model systems of spaceflight, have been shown to affect the production and activation of various cytokines including interleukins (IL) and tumor necrosis factor (TNF). Levels of urinary IL-2 are elevated on the first day of spaceflight and again after returning from space. Most results from ground-based studies in rodents indicate either no alterations in cytokines or decreased levels. Results from this experiment indicate that HP 228, a potent cytokine restraining agent (CRA (TM)) was effective in attentuating many of the disuse deconditioning changes induced by the ground-based hindlimb suspension model that simulates weightlessness in rats. HP 228 is a novel heptapeptide with unnatural amino acids and can effectively restrain lipopolysaccharide (LPS)-induced increased levels of several key cytokines, including plasma TNF alpha, IL-1 beta and IL-6. HP 228 has also been shown to be effective in several rodent models of pain, inflammation and LPS-induced lethality, as well as in reducing inducible nitric oxide synthase.
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PMID:Effectiveness of a cytokine restraining agent (CRA (TM)) in attenuating disuse deconditioning induced by hindlimb unloading in rats. 1153 92

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

Acupuncture has become quite familiar to many Koreans not only for pain, but also for many other health problems, both in acute and chronic conditions. Actually, acupuncture is a therapeutic technique that is part of a larger system of traditional oriental medicine. There are several styles of acupuncture. We investigated the regulatory effects of cytokine production in peripheral blood of asthma patients (AP) by SOOJI CHIM (Koryo Hand Acupuncture Therapy, KHT). Clinical signs of asthma disappeared markedly by KHT. The mean interleukin (IL)-2 and IL-6 plasma levels were lower in the AP group than in the normal group, whereas the mean interferon (IFN)-gamma, IL-4, and tumor necrosis factor (TNF)-alpha levels were higher in the AP group. Plasma IFN-gamma and IL-2 levels derived from T helper (Th)1 cells and IL-4 levels derived from Th2 cells were elevated in the AP group by KHT. Especially, plasma IL-6 levels derived from Th2 cells were elevated significantly in the AP group by KHT. Reduced plasma levels of TNF-alpha were observed in the AP group by KHT. Plasma IgE levels were also measured but there were no significant differences from each other. During the KHT, there were no other adverse effects. These results indicate that KHT has a good asthma treatment effect, and that its action may be due to the regulation of cytokine production.
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PMID:Regulatory effect of cytokine production in asthma patients by SOOJI CHIM (Koryo Hand Acupuncture Therapy). 1206 52

We report a 62-year old woman with orbital myositis who had a favorable response to intravenous immunoglobulin (i.v.-IG) administration in preventing disease recurrence. She had been suffering from frequent relapses of swelling and redness of the left eye with increasing pain and diplopia caused by restricted eye movement of the left eyeball. T2-weighted magnetic resonance image of the orbit showed enlargement of the left medial rectus muscle. She was treated with 1 g of methylprednisolone per day for 3 days. One mg/kg per day of oral prednisolone was subsequently started with non-steroid anti-inflammatory drugs, which resulted in improvement. However, her symptoms were aggravated while the drug was tapered off even though she used a high dose of oral prednisolone. High dose of i.v.-IG (400 mg/kg per day) was then administered for five days. Since the treatment, she has been free from recurrences of the disease for over one year, suggesting that i.v.-IG can prevent the recurrence of orbital myositis. Some reports have suggested that i.v.-IG treatment is useful to prevent recurrence of other forms of inflammatory myositis, such as dermatomyositis or polymositis. Overproduction of the pro-inflammatory cytokines (IL-1, IL-1 beta, INF-alpha) and Th1 cytokines (INF-gamma, IL-2) are related to the deterioration of these diseases. I.v.-IG treatment suppresses the production of the pro-inflammatory cytokines. In our case, serum levels of the pro-inflammatory cytokines were all normal, but the IL-4 level was elevated after the i.v.-IG treatment, suggesting that orbital myositis was probably related to the Th1 dominant disease that was suppressed by IL-4.
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PMID:[A patient of recurrent orbital myositis with good response to high-dose intravenous immunoglobulin (i.v.-i.g.) therapy]. 1242 67

Influenza and its complications account for substantial morbidity and mortality among young adults and especially among the elderly. In young adults, immunization provides 70-90% protection, while among the elderly the vaccine may be only 30-40% effective; hence the need for new, more immunogenic vaccines. We compared the safety and immunogenicity of a novel IL-2-supplemented liposomal influenza vaccine (designated INFLUSOME-VAC) with that of a commercial subunit vaccine and a commercial split virion vaccine in young adults (mean age 28 years) in the winter of 1999-2000. Seventy-three healthy young adults were randomly assigned to be vaccinated intramuscularly with the following: a commercial subunit vaccine (n = 17, group A), INFLUSOME-VAC (n = 36, group B), and a commercial split virion vaccine (n = 20, group C). The three vaccines contained equal amounts of hemagglutinin (approximately 15 microg each) from the strains A/Sydney (H3N2), A/Beijing (H1N1), and B/Yamanashi. INFLUSOME-VAC induced higher geometric mean HI titers and higher-fold increases in HI titers against all three strains, compared with the two commercial vaccines. In addition, seroconversion rates for the A/Sydney and B/Yamanashi strains were significantly higher (P < 0.05) compared with the split virion vaccine, and significantly higher for the three strains compared with the subunit vaccine (69-97% vs 35-65%, P < or = 0.02). Moreover, the anti-neuraminidase response was significantly greater (P = 0.05) in group B vs group A. INFLUSOME-VAC caused mild local pain at the injection site in a significantly higher proportion of the vaccinees (83%). Thus, INFLUSOME-VAC is an immunogenic and safe vaccine in young adults.
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PMID:Immunogenicity and safety of a novel liposomal influenza subunit vaccine (INFLUSOME-VAC) in young adults. 1260 65

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


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