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)

To investigate the association of T cell activation with clinical exacerbations of RA, we measured serum levels of soluble interleukin-2 receptors (sIL2R), a marker of T cell activation, in serial samples obtained from 23 patients with RA. sIL2R measurements were performed on sera obtained from each patient every 2 weeks for up to 60 weeks, and levels were correlated with swollen joint counts, tender joint counts, physician global assessments, patient global assessments, pain scores, Health Assessment Questionnaire Disability Index scores, and Westergren erythrocyte sedimentation rates measured simultaneously. There were no significant correlations between changes in sIL2R levels and changes in any of the other measures, nor were lead-lag relationships detected, for the group as a whole. Examination of the time courses of individual patients revealed significant positive correlations between changes in sIL2R levels and changes in swollen joint counts in five patients; significant correlations with other measures were present in three or fewer patients. sIL2R levels also varied little over the 2-week time interval of greatest clinical change in each patient. These results suggest either that clinical exacerbations of RA are not associated with changes in T cell activation or that sIL2R levels do not accurately reflect such changes.
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PMID:Serial measurement of serum interleukin-2 receptor levels in patients with rheumatoid arthritis: limited evidence for a role of T cell activation in clinical exacerbations. 760 63

A 77-year-old man was diagnosed to have diabetes. He was hospitalized for appetite loss, weight loss (6 kg/3 months) and right femoral pain. An abnormal shadow was noted on chest X-P. On admission, he was alert and there were no abnormal physical findings except limitation in the range of motion in the right lower extremity. His femoral pain was treated by a non-steroid anti-inflammatory drug (NSAID). Right femoral bone biopsy revealed angiosarcoma and staining for factor VIII, with negative staining for epithelial membrane antigen on enzyme assay. Therefore, he received systemic administration of recombinant interleukin-2 (rIL-2). rIL-2 was administered intravenously twice daily at a dose of 40 x 10(4) JRU. The total dosage of rIL-2 amounted to 1200 x 10(4) JRU, but renal failure deteriorated and he died on the 50th hospital day of his second admission. Combination of rIL-2 and NSAID may cause progression of nephropathy.
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PMID:[A case of angiosarcoma with renal failure caused by recombinant interleukin-2 (rIL-2) and non-steroid anti-inflammatory drug (NSAID)]. 777 36

We previously demonstrated that plaque-forming cell (PFC) production in the spleen of mice immunized with sheep red blood cells (SRBC) was enhanced by pain stimulation. This phenomenon was due to activation of antigen nonspecific L3T4-/Lyt-2- T lymphocytes (double-negative T cells) by the beta-adrenergic action of endogenous catecholamines released from the adrenal gland after pain stimulation. Further study also demonstrated that interleukin-2 (IL-2) production of spleen cells was enhanced in mice by pain stimulation. In this study spleen cells of BALB/c mice were cultured with Con A and SRBC, respectively, and the IL-2 level was measured by incorporation of 3H-thymidine into CTLL-2 cells during culture for 24 hours. Interleukin-2 production of spleen cells from mice given pain stimulation was significantly increased compared with spleen cells of normal mice. The IL-2 production of spleen cells of normal mice was also markedly enhanced by the mixed culture with spleen cells from pain-stimulated mice. Enhancement of IL-2 production in the spleen cells of mice given pain stimulation did not occur with anti-Thy-1.2 antibody and complement treatment, but production was maintained by treatment with anti-L3T4 antibody and complement. These data suggest that the enhanced production of IL-2 in mice given pain stimulation resulted from the activation of L3T4- T cells by endogenous catecholamines released from the adrenal gland after pain stimulation. It can be assumed that activated L3T4- T cells interact with antigen-specific L3T4+ T cells and lead to enhanced IL-2 production.
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PMID:Influence of pain stimulation on interleukin-2 production in mice. 782 12

Itching is the predominant symptom of skin disease but it is ill-understood and a challenge for future research. Even the major nerve pathways for itch, and its relationship to pain are debatable. In inflamed skin, histamine plays a major role and its mode of release from mast cells in, for example, chronic urticaria is now better appreciated. Tachykinins including substance P and cytokines including interleukin-2 are evidently important peripherally. Opioid mu-receptor-dependent processes activate inhibitory circuits in the central nervous system and regulate the extent of intensity and quality of perceived itch. It is proposed that stimulation of large areas of skin such as by scratching, generates inhibitory activity which suppresses itch excitation. Therapeutic intervention based upon understanding these regulatory processes is a real prospect.
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PMID:Pathophysiology of itching. 894 93

Primary and metastatic liver cancers have a poor prognosis. At present, sonographically guided alcohol injection results in a partial reduction of cancer masses even if severe toxic effects (including pain and bleeding) are always present. For these reasons, a pilot study was started to evaluate the feasibility of an intralesional adoptive immunotherapeutic approach, using lymphokine-activated killer (LAK) cells and recombinant interleukin-2 (rIL-2). Nine patients (one with primary hepatocarcinoma and eight with liver metastases) entered the study. Four cycles of weekly injections of LAK cells (ranging from 2 to 9 x 10(8)) and 10(6) IU rIL-2 were performed percutaneously under ultrasonic guidance. In the same period, 3 x 10(6) IU rIL-2/day, for 24 days, was injected subcutaneously. All patients but one completed the therapy. Side effects were limited to grade 1-2 fever and were mostly related to rIL-2 subcutaneous injections. No patients complained of having pain during intralesional therapy. Two complete responses were detected. One partial response, four stable diseases, and one progressive disease were observed. One patient was not evaluable. These preliminary results suggest that sonographically guided intralesional adoptive immunotherapy of liver tumors is feasible, safe, and could offer promising therapeutic advantages in cancers for which conventional treatment is generally unsatisfactory.
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PMID:Intralesional sonographically guided injections of lymphokine-activated killer cells and recombinant interleukin-2 for the treatment of liver tumors: a pilot study. 908 88

1. Although it is well known that morphine induces significant immunosuppression, the potential immunosuppressive activity of morphine derived drugs commonly used in the treatment of pain (codeine, hydromorphone, oxycodone) has never been evaluated. 2. We evaluated in the mouse the effect of the natural opiates (morphine and codeine) and synthetic derivatives (hydromorphone, oxycodone, nalorphine, naloxone and naltrexone) on antinociceptive thresholds and immune parameters (splenocyte proliferation, Natural Killer (NK) cell activity and interleukin-2 (IL-2) production). 3. Morphine displayed a potent immunosuppressive effect that was not dose-related to the antinociceptive effect, codeine possessed a weak antinociceptive effect and limited immunosuppressive activity; nalorphine, a mu-antagonist and kappa-agonist, exerted a potent immunosuppressive effect, but had very weak antinociceptive activity. The pure kappa-antagonist nor-BNI antagonized the antinociceptive, but not the immunosuppressive effect of nalorphine. 4. Hydromorphone and oxycodone, potent antinociceptive drugs, were devoid of immunosuppressive effects. 5. The pure antagonists naloxone and naltrexone potentiated immune responses. 6. Our data indicate that the C6 carbonyl substitution, together with the presence of a C7-8 single bond potentiates the antinociceptive effect, but abolishes immunosuppression (hydromorphone and oxycodone). 7. The single substitution of an allyl on the piperidinic ring resulted in a molecule that antagonized the antinociceptive effect but maintained the immunosuppressive effect. 8. Molecules that carry modifications of C6, the C7-8 bond and C14, together with an allyl or caboxymethyl group on the piperidinic ring antagonized both the antinociceptive and the immunosuppressive effect of opiates and were themselves immunostimulants.
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PMID:Antinociceptive and immunosuppressive effects of opiate drugs: a structure-related activity study. 920 56

Renal Cell Carcinoma is the third most common malignoma in urology. Only little is known about the etiology and risk factors; the age peak lies at 60 and twice as many men than women are affected. The clinical picture presents with a wide spectrum. Over one third of all tumours are detected accidentally by ultrasound or computed tomography in asymptomatic patients. Most common symptoms are hematuria and flank pain, the classical trials including in addition a palpable mass is rare and by mo means an early symptom. Paraneoplastic syndromes include unspecific (increased blood sedimentation rate, weight loss, fever) and endocrine symptoms (hypertension, polyglobulia, hypercalcemia). Diagnosis is based on imaging procedures. By means of sonography renal cysts may be separated from solid, space-occupying tumors. For the latter CT plays a decisive role for staging, therapeutic planning and prognosis. Further radiologic investigations (angiography, MRI) are indicated only in special situations. Rarely a biopsy is necessary for the distinction between renal cell carcinoma and metastases of other primary tumors. The only curative treatment of localized carcinoma is radical nephrectomy. Partial resection is indicated in cases of a single kidney, bilateral tumors and possibly also for tumors smaller than 4 cm in diameter. Radiotherapy is only initiated for palliation of painful skeletal metastases. In case of distant metastases--mainly pulmonary--nephrectomy should only be performed if systemic treatment is planned or if local complaints (pain, hematuria leading to anemia) exist. Chemotherapeutic drugs have no influence on survival. The effect of gestagens on life quality is questionable. Adoptive immunotherapy with cytokines (Interferon-alpha, interleukin-2) appears most promising. These substances, however, not yet been introduced into routine therapy should only be used in prospective studies. Furthermore, renal cell carcinoma is a potential candidate for gene therapy. After tumor nephrectomy follow-up investigations should be performed twice a year, because of the possibility of curative surgical treatment of late solid metastases. Prognosis of tumors restricted to the organ is good. Five year survival after operation is about 90%. However, is distant metastases exist already at the time of diagnosis 5 year survival drops to less than 10%.
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PMID:[Renal cell carcinoma--a current review]. 931 11

Adoptive immunotherapy (AI) with interleukin-2 (IL-2) and lymphokine-activated killer cells (LAK) is an antineoplastic modality in which immune-activated cells are administered to a host with advanced cancer in an attempt to mediate tumor regression. Levamisole (LEV), an immune stimulant, has been suggested to have therapeutic effectiveness in a variety of cancers. After a phase I trial of recombinant IL-2 plus LEV, a phase II trial of this combination was conducted in patients with advanced malignant melanoma. Nineteen patients were entered in the trial. They received IL-2 at 3 x 10(6) U/m2 subcutaneously daily x 5 plus LEV 50 mg/ m2 orally three times daily (p.o. t.i.d.) x 5. Patients were reevaluated at four-week intervals. None of the patients achieved a partial or complete regression (PR, CR). The median time to treatment failure (refusal, progression, or off study due to toxicity) was 56 days. Grade IV toxicities included vomiting (3 patients), lethargy (1 patient), and musculoskellar pain (1 patient). This regimen is not recommended for further testing in patients with advanced malignant melanoma.
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PMID:Phase II study of combined levamisole with recombinant interleukin-2 in patients with advanced malignant melanoma. 934 34

This study evaluated the initial promise of a dual-pathway conceptual model linking daily event stressors to rheumatoid arthritis (RA) disease activity through changes in immune system activation and mood. Fifty individuals, who were studied on five occasions two weeks apart, reported daily event stressors on the Daily Life Experience Checklist, daily mood on an abbreviated version of the Profile of Mood States-B, and daily joint pain on the Rapid Assessment of Disease Activity in Rheumatology. Serial clinical examinations comprised ratings of joint tenderness and swelling, and blood drawn during exams was analyzed for sedimentation rate (an indicator of systemic inflammation) and soluble interleukin-2 receptors (a marker of immune system activation known to correlate with RA disease activity). Across-person analyses failed to establish links from daily event stressors to either disease activity or composites of joint pain and joint inflammation when associations were adjusted for the effect of neuroticism on self-report measures. Pooled within-person analyses, however, were generally consistent with the relations predicted by the dual-pathway model. Increases in daily event stressors during the week preceding each clinical exam were associated with increased joint pain (regardless of changes in mood). At the same time, increased daily stressors were indirectly associated with decreased joint inflammation through reduction in levels of soluble interleukin-2 receptors. The dual-pathway model, which may be limited to short-term psychological and psychoimmunologic processes, underscores the importance of distinguishing potentially opposing effects of stress on pain versus inflammation in individuals with rheumatoid arthritis.
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PMID:A dual pathway model of daily stressor effects on rheumatoid arthritis. 960 91

We investigated the effects of (+)-4-[(alpha R)-alpha-((2S, 5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N, N-diethylbenzamide (SNC 80), a nonpeptidic delta-opioid receptor-selective agonist, on rat leukocyte functions. Intracerebroventricular injection of SNC 80 (20 nmol) in Fischer 344N male rats did not affect splenic natural killer cell activity compared with intracerebroventricular saline-injected controls. SNC 80 also had no effect on concanavalin A-, anti-T cell receptor-, interleukin-2- and anti-T cell receptor + interleukin-2-induced splenic and thymic lymphocyte proliferation in most experiments. In some experiments, however, SNC 80 significantly (P < .01) caused a 41 to 93% increase of concanavalin A-, anti-T cell receptor-, interleukin-2- and anti-T cell receptor + interleukin-2-induced splenic lymphocyte proliferation compared to controls. Additionally, SNC 80 did not significantly affect splenic T cell or natural killer cell populations as measured by the expression of T cell receptoralphabeta, and T helper (CD4), T suppressor/cytotoxic (CD8) and natural killer cell surface markers. Finally, SNC 80 did not affect interferon-gamma- or lipopolysaccharide (LPS)-induced splenic nitric oxide, and LPS-induced tumor necrosis factor-alpha production by splenic macrophages. These results suggest that SNC 80 could be useful in the treatment of pain without suppressing immune function. However, the potential immunoenhancing properties of SNC 80 may be also valuable in immunocompromised individuals.
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PMID:Rat natural killer cell, T cell and macrophage functions after intracerebroventricular injection of SNC 80. 969 52


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