Skip to main content
Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 1978 Jun;37(3):212–217. doi: 10.1136/ard.37.3.212

Combination of theophylline and prostaglandin E1 as inhibitors of the adjuvant-induced arthritis syndrome of rats.

I L Bonta, M J Parnham, L Van Vliet
PMCID: PMC1000209  PMID: 308353

Abstract

The effects of daily subcutaneous administration of prostaglandin E1 (PGE1), theophylline, and of both drugs together were studied on the Freund's adjuvant-induced inflammatory and arthritic syndrome in rats. In the doses used, neither drug affected the acute inflammatory response in the adjuvant-treated paw, but together they caused marked inhibition. Chronic inflammation in the contralateral (nontreated) hind paws was slightly inhibited by each drug and combined treatment resulted in marked inhibition. The drugs also counteracted splenomegaly in adjuvant-diseased rats and their effects on spleen weight paralleled the inhibition of chronic inflammation. Arthritic lesions, as judged by x-rays of tibiotarsal joint destruction in the nontreated paws, were partially prevented by PGE1 alone, but not by theophylline. The combined treatment entirely prevented these joint lesions. PGE1 did not cause an increase in adrenal weight, but enhanced the effect of theophylline on adrenal weight. Only PGE1 improved gait in arthritic rats, simultaneous theophylline treatement having little additional effect. Other workers have found the PGE1 increases intracellular cAMP and that this effect is enhanced by the phosphodiesterase inhibitor, theophylline. We propose that the anti-inflammatory and anti-arthritic effects of combined drug treatment involve cAMP changes in phagocytic cells at the site of tissue injury and in systemic lymphocytes.

Full text

PDF
212

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aspinall R. L., Cammarata P. S. Effect of prostaglandin E2 on adjuvant arthritis. Nature. 1969 Dec 27;224(5226):1320–1321. doi: 10.1038/2241320a0. [DOI] [PubMed] [Google Scholar]
  2. Bonta I. L., Parnham M. J., van Vliet L., Vincent J. E. Mutual enhancement of the effects of prostaglandin E1 and theophylline on the Freud adjuvant-induced arthritis syndrome of rats [proceedings]. Br J Pharmacol. 1977 Mar;59(3):438P–439P. [PMC free article] [PubMed] [Google Scholar]
  3. Bourne H. R., Lichtenstein L. M., Melmon K. L., Henney C. S., Weinstein Y., Shearer G. M. Modulation of inflammation and immunity by cyclic AMP. Science. 1974 Apr 5;184(4132):19–28. doi: 10.1126/science.184.4132.19. [DOI] [PubMed] [Google Scholar]
  4. Bourne H. R., Lichtenstein L. M., Melmon K. L. Pharmacologic control of allergic histamine release in vitro: evidence for an inhibitory role of 3',5'-adenosine monophosphate in human leukocytes. J Immunol. 1972 Mar;108(3):695–705. [PubMed] [Google Scholar]
  5. DiPasquale G., Rassaert C., Richter R., Welaj P., Tripp L. Influence of prostaglandins (Pg) E2 and F2 on the inflammatory process. Prostaglandins. 1973 Jun;3(6):741–757. doi: 10.1016/0090-6980(73)90001-4. [DOI] [PubMed] [Google Scholar]
  6. Glenn E. M., Rohloff N. Antiarthritic and antiinflammatory effects of certain prostaglandins. Proc Soc Exp Biol Med. 1972 Jan;139(1):290–294. doi: 10.3181/00379727-139-36128. [DOI] [PubMed] [Google Scholar]
  7. Gordon D., Bray M. A., Morley J. Control of lymphokine secretion by prostaglandins. Nature. 1976 Jul 29;262(5567):401–402. doi: 10.1038/262401a0. [DOI] [PubMed] [Google Scholar]
  8. Henney C. S., Bourne H. R., Lichtenstein L. M. The role of cyclic 3',5' adenosine monophosphate in the specific cytolytic activity of lymphocytes. J Immunol. 1972 Jun;108(6):1526–1534. [PubMed] [Google Scholar]
  9. Klein D. C., Raisz L. G. Prostaglandins: stimulation of bone resorption in tissue culture. Endocrinology. 1970 Jun;86(6):1436–1440. doi: 10.1210/endo-86-6-1436. [DOI] [PubMed] [Google Scholar]
  10. Lichtenstein L. M., Gillespie E., Bourne H. R., Henney C. S. The effects of a series of prostaglandins on in vitro models of the allergic response and cellular immunity. Prostaglandins. 1972 Dec;2(6):519–528. doi: 10.1016/s0090-6980(72)80040-6. [DOI] [PubMed] [Google Scholar]
  11. Morley J. Prostaglandins and lymphokines in arthritis. Prostaglandins. 1974 Nov 25;8(4):315–326. doi: 10.1016/s0090-6980(74)80096-1. [DOI] [PubMed] [Google Scholar]
  12. PEARSON C. M. EXPERIMENTAL MODELS IN RHEUMATOID DISEASE. Arthritis Rheum. 1964 Feb;7:80–86. doi: 10.1002/art.1780070111. [DOI] [PubMed] [Google Scholar]
  13. Parnham M. J. Metyrapone: a possible tool in investigating the role of endogenous corticosteroids in inflammation. Agents Actions Suppl. 1977;2:85–97. doi: 10.1007/978-3-0348-7177-8_8. [DOI] [PubMed] [Google Scholar]
  14. Parnham M. J., Shoshan S., Bonta I. L., Neiman-Wollner S. Increased collagen metabolism in granulomata induced in rats deficient in endogenous prostaglandin precursors. Prostaglandins. 1977 Oct;14(4):709–714. doi: 10.1016/0090-6980(77)90198-8. [DOI] [PubMed] [Google Scholar]
  15. Ryzewski J. The effect of stimulation and inhibition of the autonomic nervous system on the development and course of polyarthritis induced with Freund's adjuvant in rats. Pol Med J. 1966;5(5):1011–1018. [PubMed] [Google Scholar]
  16. Scott R. E. Effects of prostaglandins, epinephrine and NaF on human leukocyte, platelet and liver adenyl cyclase. Blood. 1970 Apr;35(4):514–516. [PubMed] [Google Scholar]
  17. Van Arman C. G. Pathway to adjuvant arthritis. Fed Proc. 1976 Nov;35(13):2442–2446. [PubMed] [Google Scholar]
  18. Weissmann G., Goldstein I., Hoffstein S. Prostaglandins and the modulation by cyclic nucleotides of lysosomal enzyme release. Adv Prostaglandin Thromboxane Res. 1976;2:803–814. [PubMed] [Google Scholar]
  19. Zurier R. B., Hoffstein S., Weissmann G. Suppression of acute and chronic inflammation in adrenalectomized rats by pharmacologic amounts of prostaglandins. Arthritis Rheum. 1973 Sep-Oct;16(5):606–618. doi: 10.1002/art.1780160505. [DOI] [PubMed] [Google Scholar]
  20. Zurier R. B., Quagliata F. Effect of prostaglandin E 1 on adjuvant arthritis. Nature. 1971 Dec 3;234(5327):304–305. doi: 10.1038/234304a0. [DOI] [PubMed] [Google Scholar]

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Publishing Group

RESOURCES