Circadian variation in disease activity in rheumatoid arthritis.

Harkness, J.; Richter, M.; Panayi, G. S.; Pette, K Van de; Unger, A; Pownall, R; Geddawi, M.

doi:10.1136/bmj.284.6315.551

Cited by 160 publications

(92 citation statements)

References 9 publications

(1 reference statement)

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“…On the basis of the work described here, we propose that induction of low but sustained elevations in plasma cortisol could be an effective treatment for RA. Furthermore, it could be argued that intensive but short-term therapy with cortisol at the onset of RA may abort the subsequent development of the chronic phase of the disease, as has been demonstrated for SCW arthritis in the LEWIN rat (10). Finally, the studies described here suggest that an abnormality in the immune/inflammatory and neuroendocrine loop in patients with RA may be an additional and hitherto unsuspected factor in the immunopathogenesis of this disease.…”

Section: Discussionmentioning

confidence: 86%

“…This situation may pertain to RA since it has a pronounced diurnal periodicity of disease activity thought to be dependent on the circadian rhythm of physiologic levels of glucocorticoids (10,11). In addition, work by Neeck et al has shown that although the plasma cortisol concentration in RA is within the normal range, it is inappropriately low for the degree of ongoing inflammation (12).…”

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confidence: 99%

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Defective hypothalamic response to immune and inflammatory stimuli in patients with rheumatoid arthritis

Chikanza

Petrou

Kingsley

et al. 1992

Arthritis & Rheumatism

336

163

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Objective. To determine the integrity of the hypothalamic-pituitary-adrenal (HPA) axis responses to immune/inflammatory stimuli in patients with rheumatoid arthritis (RA).Methods. Diurnal secretion of cortisol and the cytokine and cortisol responses to surgery were studied in subjects with active RA, in subjects with chronic osteomyelitis (OM), and in subjects with noninflammatory arthritis, who served as controls.Results. Patients with RA had a defective HPA response, as evidenced by a diurnal cortisol rhythm of secretion which was at the lower limit of normal in contrast to those with OM, and a failure to increase cortisol secretion following surgery, despite high levels of interleukin-Ijl (IL-lm and IL-6. The corticotropinreleasing hormone stimulation test in the RA patients showed normal results, thus suggesting a hypothalamic defect, but normal pituitary and adrenal function.Conclusion. These findings suggest that RA patients have an abnormality of the HPA axis response to

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Section: Discussionmentioning

confidence: 86%

mentioning

confidence: 99%

Defective hypothalamic response to immune and inflammatory stimuli in patients with rheumatoid arthritis

Chikanza

Petrou

Kingsley

et al. 1992

Arthritis & Rheumatism

336

163

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“…gene within the joitit [29]; treatment of these animals with MoAbs to TNF-a completely abrogated the arthritis [29]. In RA, there is a diurnal rhythm of disease activity [30]. We therefore set out to study the 24-h secretion pattern of TNF-a, TNF-sR55 and TNF-sR75 in patients with active RA.…”

Section: Introductionmentioning

confidence: 99%

Tumour necrosis factor soluble receptors behave as acute phase reactants following surgery in patients with rheumatoid arthritis, chronic osteomyelitis and osteoarthritis

Chikanza

Roux‐Lombard

Dayer

et al. 1993

Clinical and Experimental Immunology

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SUMMARY Tumour necrosis factor‐alpha (TNF‐α) is involved in diverse biological processes including immune and inflammatory reactions and the response to surgical stress. Two soluble TNF receptor protein fragments. TNF‐sR55 (from the p55 kD TNF receptor) and TNF‐sR75 (from the p75 kD TNF receptor), are released by cells during inflammation and may modulate the effects of TNF‐α. We have studied the kinetics of secretion of TNF‐α, TNF‐sR55 and TNF‐sR75 in the sera of patients with rheumatoid arthritis (RA) and control subjects with osteoarthritis (OA) or chronic osteomyelitis (OM) before and after major surgery. Significantly higher pre‐operative levels of TNF‐sR55 and TNF‐sR75 were found in RA and OM as compared with OA (P<0.02). Following surgery, TNF‐sR55 increased within 24 h in RA, OM and OA (P<0.05), whereas TNF‐sR75 increased significantly only in OM and OA patients (P<0.05). By contrast, no TNF‐α was detectable before and after surgery in any of the subjects, but this may have been due to impaired detection (by ELISA) of TNF‐α when it is bound to TNF‐sR. These findings suggest that TNF‐sR55 and TNF‐sR75 may be further markers of the host's reaction to inflammatory insults. They may also play a role in modulating the immune and inflammatory reactions by inhibiting the systemic effects of TNF‐α.

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“…In rheumatoid arthritis, the peak of disease activity occurs at about 3 AM, and minimal activity occurs 12 hours later. 46 Similarly, the greatest probability of renal allograft rejection occurs between 5 and 8 AM. 47 Those findings may be linked to the seemingly greater immune system activity during this period and may possibly be influenced by the occurrence of low concentrations of immunosuppressive agents, such as corticosteroids, during this critical interval.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and pharmacodynamics of methylprednisolone when administered at 8 AM versus 4 PM

Fisher

Ludwig

Wald

et al. 1992

Clin Pharmacol Ther

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The temporal variations in the pharmacokinetics and pharmacodynamics of methylprednisolone at 8 AM versus 4 PM were investigated in six healthy male volunteers. Subjects completed three phases: no drug administration, 20 mg intravenous methylprednisolone at 8 AM, and the same dose at 4 PM. Methylprednisolone clearance was 28% greater in the afternoon. The suppressive effects of methylprednisolone on basophils (measured as whole blood histamine), helper T lymphocytes, and cortisol concentrations, assessed by the ratio of the area under the curve (AUC) after methylprednisolone to the baseline AUC, were not different between the phases. The 50% inhibitory concentration values for methylprednisolone derived from pharmacodynamic models were also similar, indicating no difference in intrinsic responsiveness. However, cortisol concentrations returned to baseline about 4 hours earlier after the 4 PM compared with the 8 AM dose because of the enhanced afternoon methylprednisolonc clearance. These findings are in agreement with other studies that suggest adequate clinical effects and less disturbance of cortisol circadian behavior when methylprednisolone is administered as a single dose in the morning.Corticosteroids are an important class of therapeutic agents because of their antiinflammatory and immuno-suppressive properties. Ideal dosing regimens have yet to be elucidated for the treatment of numerous disease states. Currently, corticosteroids are most often administered as a single morning dose. However, these agents may be administered as divided doses or even as a single evening dose in those conditions requiring adrenal suppression. 1 Numerous drugs, including theophylline, 2 phenyloin, 3 and cisplatin, 4 have demonstrated temporal variations in their pharmacokinetics. This is not surprising because it has been shown in animals that both hepatic drug-metabolizing activities and renal clearance (CL R ) mechanisms exhibit circadian variations. 5,6 Human chronopharmacokinetic studies with exogenous corticosteroids are limited. Prednisolone has been evaluated in three studies with conflicting findings. The first study 7 found no circadian differences in prednisolone Copyright © 1992 clearance, volume of distribution (V), or half-life (t ½ ). The second study 8 found circadian differences in the clearance (CL) of free prednisolone and the free fraction when it was given as a low dose. The third study 9 found circadian variation in all parameters investigated. To date, no human chronopharmacokinetic study with methylprednisolone has been reported. In male Norwegian rats, the maximum methylprednisolone t ½ was noted to occur when the drug was administered at 6 PM, the commencement of the nocturnal activity period of the animals, whereas the shortest t ½ was documented with noon administration, or midway through the diurnal rest span. 10 The pharmacodynamics of exogenous corticosteroids may show temporal variations. The susceptibility of the hypothalamic-pituitary-adrenal axis to suppression in humans, as measured...

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Circadian variation in disease activity in rheumatoid arthritis.

Cited by 160 publications

References 9 publications

Defective hypothalamic response to immune and inflammatory stimuli in patients with rheumatoid arthritis

Defective hypothalamic response to immune and inflammatory stimuli in patients with rheumatoid arthritis

Tumour necrosis factor soluble receptors behave as acute phase reactants following surgery in patients with rheumatoid arthritis, chronic osteomyelitis and osteoarthritis

Pharmacokinetics and pharmacodynamics of methylprednisolone when administered at 8 AM versus 4 PM

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