Migration of interleukin-6 producing Langerhans cells to draining lymph nodes following skin sensitization.
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Animals↗
Biomedical subjects
S J Hopkins
Publications and source records attributed to S J Hopkins.
Cytokines and the nervous system II: Actions and mechanisms of action.
Cytokines exert diverse actions on the PNS and the CNS and have been implicated in neuronally mediated responses to disease and injury. Certain cytokines participate in the central control of host systemic responses to disease, acting as signals to and within the brain. These molecules are also involved in neuronal degeneration and repair in the PNS and CNS, and have been proposed as mediators of various neuropathologies. The actions, mechanisms of action and potential strategies for modifying cytokines in the nervous system will be considered in this review, which continues the discussion of cytokine expression and recognition published in the February issue of TINS.
Animals↗
Multiple mechanisms mediate antipyretic action of glucocorticoids.
Glucocorticoids inhibit various components of the acute phase response, particularly the increase in body temperature (fever) induced by a variety of stimuli. In the present study these observations have been extended, and we have determined the effect of glucocorticoid treatment or surgical adrenalectomy on the cytokine and prostaglandin (PG) concentrations in plasma and cerebrospinal fluid (CSF) during the febrile response to endotoxin. Dexamethasone treatment, either before or after endotoxin injection, markedly inhibited fever and the increased plasma interleukin (IL)-6 and CSF IL-6, PGE2, and PGF2 alpha concentrations. Adrenalectomized (ADX) rats showed higher fevers and plasma and CSF IL-6, PGE2, and PGF2 alpha, concentrations compared with sham-operated animals and exhibited a lower plasma-to-CSF IL-6 ratio than sham-operated animals. Dexamethasone pretreatment also inhibited fever induced by centrally injected TNF-alpha, IL-1 beta, or IL-6. Pyrogenic response to IL-8 was not modified by indomethacin but was markedly inhibited by prior treatment with dexamethasone. These results support the hypothesis that endogenous glucocorticoids function as part of an inhibitory feedback system involved in the modulation of fever and that multiple mechanisms may be involved in their antipyretic effect.
Adrenalectomy↗
Cytokines and the nervous system. I: Expression and recognition.
Cytokines are a heterogeneous group of polypeptide mediators that have been associated classically with activation of the immune system and inflammatory responses. An increasing number of related mediators is now included in this category and most of them have been shown to act on a variety of tissues, including the PNS and CNS. Cytokines and their receptors are expressed in tissues of these nervous systems, and might derive from invading immune, or resident, cells. Trauma in peripheral tissues might also induce cytokine-mediated events in the CNS, via either the circulation or secondary induction within the brain. In this first of a two-part review, the general properties, expression and recognition of these cytokines with respect to the nervous system are discussed.
Animals↗
Identification of dendritic cells as a major source of interleukin-6 in draining lymph nodes following skin sensitization of mice.
Skin sensitization with chemical allergens is associated with the activation and proliferation of T lymphocytes within lymph nodes draining the site of exposure. These events are accompanied by the secretion of interleukin-6 (IL-6) by lymph node cells (LNC). We have investigated the cellular source of IL-6 seventy-two hours following primary exposure of mice to the contact allergen oxazolone. Immunocytochemical analyses of sections of activated lymph nodes have revealed that cells expressing IL-6 are located within the T-dependent lymph node paracortex, with none present in lymphoid follicles. Cells which expressed IL-6 cofractionated exclusively with LNC of low buoyant density, the majority of which also expressed membrane Ia and had a dendritic morphology. Depletion of dendritic cells from LNC culture was associated with a significant decrease in the secretion of IL-6 by the residual population. These data demonstrate that dendritic cells are a major source of IL-6 within lymph nodes during primary immune responses to cutaneous antigens.
Animals↗
Mechanisms of activation of the pituitary-adrenal axis by tissue injury in the rat.
To characterize the mechanisms of the pituitary-adrenal (P-A) response to tissue injury, rats were injected intramuscularly (IM) with turpentine. This resulted in marked elevations in the plasma concentrations of ACTH and corticosterone within the first hour after injection, which were attenuated by either total deafferentation of the medial basal hypothalamus (MBH) or neonatal capsaicin pretreatment. The plasma concentrations of corticosterone remained elevated for 18 h in the turpentine-injected rats, despite a return of ACTH toward control values (by 2-4 h). Bioactive concentrations of interleukin-6 (IL-6) in plasma rose markedly after turpentine, and its concentrations were significantly correlated with plasma corticosterone concentrations 4-8 h after turpentine. Pretreatment with IL-1 receptor antagonist (IL-1ra) attenuated the release of IL-6 and had a marginal effect on the corticosterone response 6 h after turpentine. These results suggest that the early and late phase of the P-A response to tissue injury are mediated by different mechanisms.
Acute-Phase Reaction↗
Tumor necrosis factor-alpha and fever after peripheral inflammation in the rat.
The involvement of endogenous tumor necrosis factor-alpha (TNF-alpha) in the pyrogenic [i.e., rise in colonic temperature (Tc)] and thermogenic [increase in oxygen consumption (VO2)] responses to inflammation was investigated in rats subjected to an intramuscular injection of turpentine. Turpentine administration caused a rise in Tc and VO2 within 2 h (0.9 +/- 0.1 degrees C, 27 +/- 2%, respectively). Eighteen to twenty hours after turpentine, the magnitude of these responses had increased (2.3 degrees C fever and a 28% increase in metabolic rate compared with control animals) and was associated with marked inflammation in the injected limb. A rapid (by 4 h) and sustained rise in the plasma concentration of the endogenous pyrogen IL-6, but not TNF-alpha, was also observed. Intravenous pretreatment with a TNF-alpha antiserum attenuated the rise in Tc observed 2, 8, and 18 h after turpentine injection and almost abolished the hypermetabolic response observed at 18 h. In addition, the TNF-alpha antiserum inhibited the peak rise (8 h) in plasma IL-6 by 76%. These findings indicate that endogenous TNF-alpha is involved in fever and hypermetabolism during inflammation and that it may exert these effects by inducing the release of IL-6 into circulation.
Animals↗
Interleukin-6 production by draining lymph node cells following primary contact sensitisation of mice: relationship to the proliferative response.
Interleukin-6 (IL-6) production and proliferative responses by draining lymph node cells were studied in mice exposed topically to a series of chemicals. Chemicals with the capacity to induce sensitisation, but not non-sensitisers, promoted both IL-6 production and lymph node cell proliferation ex vivo. The responses exhibited similar kinetics, were dependent upon the dose of topically applied allergen, and correlated significantly. We demonstrate that the main source of IL-6 within draining lymph nodes is not proliferating T lymphocytes. The induction of a strong IL-6 response, and the relationship of this to cellular proliferation indicate that production of this cytokine within the lymph node is closely associated with the induction of contact sensitivity in mice.
Animals↗
The kinetics of cytokine production by draining lymph node cells following primary exposure of mice to chemical allergens.
Skin sensitization with chemical allergens is associated with the activation and proliferation of lymphocytes in lymph nodes draining the site of exposure. As lymphocyte activation is regulated by the action of cytokines, we have investigated the nature and kinetics of cytokine production by draining lymph node cells (LNC) from mice, following their primary exposure to chemical allergens. Both interleukin-1 (IL-1) and IL-6 were induced in a biphasic manner following primary exposure of mice to oxazolone or to dicyclohexylmethane-4,4'-diisocyanate (HMDI). The initial phase of production occurred when LNC were prepared from mice 8-20 hr following exposure, while the second peak was coincident with the maximal proliferative response at 72 hr. Increased IL-4 production was observed only when LNC were prepared 96 hr following sensitization. Despite vigorous lymphocyte proliferation there was no evidence for IL-2 production by draining LNC. The ordered and transient pattern of cytokine production that occurs during the afferent phase of contact sensitization suggests that sequential cytokine signals may be involved in regulating the characteristics of the response generated within the draining lymph node.
Allergens↗
Importance of brain IL-1 type II receptors in fever and thermogenesis in the rat.
Interleukin-1 (IL-1) acts centrally to induce fever and thermogenesis in rodents. The central actions of IL-1 alpha and IL-1 beta apparently involve different mechanisms, and the effects of IL-1 beta are not consistent with interaction with a type I (IL-1RI) 80-kDa receptor. In the present study the involvement of the type II IL-1 receptor (IL-1RII) was tested in the rat by examining the effects of central injection of a monoclonal antibody (ALVA-42), which blocks the IL-1RII. Pretreatment of rats with ALVA-42 (6 micrograms icv) inhibited the thermogenic and pyrogenic responses to intracerebroventricular injection of 5 ng (but not 50 ng) of IL-1 beta in conscious rats but did not significantly modify responses to IL-1 alpha. ALVA-42 also failed to modify the responses to peripherally administered IL-1 beta (1 microgram) but significantly attenuated the pyrogenic and thermogenic responses to peripheral (125 micrograms) or central (1 microgram) injection of endotoxin. These data indicate that IL-1RII mediates the central effects of a low dose of IL-1 beta, but not IL-1 alpha, on fever and thermogenesis in the rat. They also imply that responses to endotoxin are due, at least in part, to the activation of IL-1RII by IL-1 beta released within the brain and that effects of peripherally injected IL-1 beta involve different mechanisms, probably associated with IL-1RI.
Animals↗
A controlled trial of a single dose of azithromycin for the treatment of chlamydial urethritis and cervicitis. The Azithromycin for Chlamydial Infections Study Group.
BACKGROUND: Currently, there is no single-dose therapy that is effective in the treatment of urethral or endocervical infections with Chlamydia trachomatis. Azithromycin is a new azalide antibiotic that has substantial activity against C. trachomatis, is concentrated intracellularly, and has a long half-life in serum and tissue. METHODS: We conducted a trial in which 299 female patients and 158 male patients with uncomplicated genital infection and a positive C. trachomatis antigen test were randomly assigned to receive either azithromycin (1 g once orally) or doxycycline (100 mg orally twice daily for seven days). Only patients subsequently determined to have a culture positive for C. trachomatis at base line were included in the evaluation of efficacy. RESULTS: Among the patients who could be evaluated, 5 of the 141 patients (4 percent) treated with azithromycin did not respond to treatment, as compared with 3 of the 125 patients (2 percent) treated with doxycycline (difference between groups, 2 percent; 95 percent confidence interval, 0 to 6 percent). Of the patients evaluated 21 to 35 days after treatment, none of 112 treated with azithromycin and 1 of 102 treated with doxycycline had a positive culture. The rates of bacteriologic cure were similar for the 98 female patients (97 percent) and the 43 male patients (95 percent) treated with azithromycin. Seventeen percent of the patients who received azithromycin and 20 percent of those treated with doxycycline had mild-to-moderate drug-related side effects, mainly gastrointestinal symptoms. CONCLUSIONS: A single 1-g dose of azithromycin is as effective for the treatment of uncomplicated genital chlamydial infections as a standard seven-day course of doxycycline.
Adolescent↗
Cytokine inter-relationships and their association with disease activity in arthritis.
In order to investigate the relationships between cytokine production and arthritic disease we have determined the concentrations of immunoreactive interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, tumour necrosis factor-alpha (TNF-alpha), interferon-alpha (IFN-alpha), IFN-gamma, and soluble IL-2-receptor (sIL-2R), as well as bioactive IL-1 and IL-6, in synovial fluids (SF) and plasma of patients with a variety of arthritides. Careful assay revealed only minimal concentrations of IL-1, particularly its biologically active form, in SF. No IL-1 was detectable in the plasma of patients that had IL-1 in their SF. Concentrations of both immunoreactive IL-1 beta and TNF-alpha in SF of rheumatoid arthritis (RA) patients were significantly higher than those in SF from patients with other inflammatory arthritides or osteoarthritis (OA). IL-6 and sIL-2R concentrations in both SF and plasma were higher in RA patients than in OA patients, and were significantly correlated. Approximately half of the SF from patients with all arthropathies contained detectable IFN-alpha, whilst IFN-Y was present in less than 10%. There were significant associations between IL-6, sIL-2R, IL-1 beta, TNF-alpha and IFN-alpha. The concentration of these cytokines, where detectable, was also related to leukocyte counts in the SF, as well as to parameters assessing local and systemic disease activity. Although IL-6 was the cytokine most clearly related to other cytokines, and to parameters assessing disease activity, the relationship between general articular disease activity and IL-6 was only evident in patients with arthropathies other than rheumatoid arthritis.
Arthritis↗
Relationships between local inflammation, interleukin-6 concentration and the acute phase protein response in arthritis patients.
Interleukin-6 (IL-6) concentrations in knee joint synovial fluids and paired plasma samples of arthritis patients were examined with respect to each other and parameters of the inflammatory response. Synovial fluid and plasma IL-6 concentrations were significantly higher in patients with inflammatory arthritis than those detected in patients with osteoarthritis (P less than 0.001). The IL-6 concentrations in synovial fluids were considerably higher than, but significantly correlated with (r = 0.65; P less than 0.001), those of plasma. Furthermore, synovial fluid IL-6 concentrations in bilaterally inflamed knees were significantly correlated (r = 0.79; P less than 0.001) and there was a significant correlation with the extent of inflammatory cell infiltrate (r = 0.75; P less than 0.001). In unselected rheumatoid arthritis patients there was only a weak correlation between IL-6 and plasma C-reactive protein (CRP) concentration, and no correlation between IL-6 and erythrocyte sedimentation rate (ESR). However, both ESR and CRP concentration were highly correlated with plasma IL-6 concentration in patients with other inflammatory arthritides, particularly psoriatic and HLA B27 positive spondyloarthritis (r = 0.72-0.94; P less than 0.005). These relationships suggest that IL-6 production in inflammed knee joints can be a significant determinant of acute phase protein responses in arthritis patients, although the situation in patients with rheumatoid arthritis is more complex and may be influenced by other disease-related factors.
Acute-Phase Reaction↗
Interleukin-6 is a centrally acting endogenous pyrogen in the rat.
Intracerebroventricular (i.c.v.) injection of human recombinant interleukin-6 (IL-6; 20-100 ng) caused significant increases in colonic temperature and resting oxygen consumption (VO2) in conscious rats. These effects were prevented by pretreatment with a cyclooxygenase inhibitor (flurbiprofen, 1 mg/kg, i.p.) or a corticotrophin-releasing factor antagonist (alpha-helical CRF9-41, 25 micrograms, i.c.v.). Higher doses of IL-6 (i.c.v.) caused only small changes in VO2 and temperature, and very high doses given intravenously (i.v.) (4 micrograms/kg) were required to stimulate these parameters. Central injection of anti-rat IL-6 antibody inhibited the effects of interleukin-1 beta (i.c.v.) or endotoxin injection (i.p.) on colonic temperature and VO2 in conscious rats. These data indicate that IL-6 is an important endogenous pyrogen that acts within the central nervous system.
Animals↗
Bioassay of interleukin-1 in serum and plasma following removal of inhibitory activity with polyethylene glycol.
Serum and plasma normally inhibit the responsiveness of the indicator cells used in bioassays for interleukin-1 (IL-1). A precipitation step with 12% polyethylene glycol (PEG) was found to remove material responsible for such inhibition. The IL-1 bioassay could be performed in the presence of a 3% concentration of PEG and recovery of added natural IL-1 from plasma or serum was essentially complete.
Animals↗
Challenges for continuing education of public health nurses in Florida.
Perceived continuing education needs among public health nurses at the staff and supervisory levels were investigated. A questionnaire was adapted for each and administered at participating county public health units. Results indicated a high level of agreement between staff nurses and supervisors. Further analysis of the data suggested a relationship between the nurses' perception of continuing education needs and the realities of their nursing practice. Public health nurses, educators, and administrators face the challenge of refocusing continuing education needs and activities on the broad scope of this area of specialty.
Adult↗
Cytokines and eicosanoids in rheumatic diseases.
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Biological Factors↗