Kinetics of the effect of a single dose of cyclosporin-A on antibody and cell mediated immune responses in the guinea pig

Parker, Darien; Drössler, K; Turk, J.L.

doi:10.1016/0192-0561(84)90037-7

Cited by 22 publications

(9 citation statements)

References 8 publications

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“…Conversely, it increased the pro liferative response to ConA; such an immunostimulatory effect of cyclosporine at low doses has been seen before [33,34], These effects of cyclosporine were counteracted by pituitary grafts, indicating an antagonistic in teraction of cyclosporine and prolactin. More over, in pituitary-grafted rats, cyclosporine decreased ConA-induced proliferation, sug gesting that synergistic effects of cyclosporine and prolactin may also occur.…”

Section: Discussionmentioning

confidence: 81%

Effect of Cyclosporine on Immune Responses in Submaxillary Lymph Nodes of Pituitary-Grafted Rats

Arce

Castrillón²,

Della‐Maggiore³

et al. 1996

Neurosignals

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This work was undertaken to analyze the interrelationships between prolactin and cyclosporine in affecting immune responsiveness in submaxillary lymph nodes. Male rats received an anterior pituitary graft within breast muscles on day 5, or under the kidney capsule, on day 30 or 60 of life. On day 70 (rats operated on day 5 or 30) or on day 100 (rats operated on day 60) animals were injected with Freund''s complete adjuvant and cyclosporine (5 mg/kg for 5 days), and were killed 2 days after immunization. Natural killer (NK) activity in submaxillary lymph node decreased in neonatally pituitary-grafted rats and increased in rats grafted on day 30 or 60, as did lymph node cellularity. Lipopolysaccharide (LPS)- and concanavalin A (ConA)-induced proliferation diminished in lymph nodes of rats grafted on day 30 or 60, respectively. Cyclosporine treatment diminished lymph node cell number and NK activity and increased the proliferative response to ConA. Cyclosporine depressive effect on lymph node cellularity was counteracted by the presence of a pituitary graft, as were the inhibition of NK activity and the stimulatory effect on ConA-induced cell proliferation. In pituitary-grafted rats, cyclosporine decreased submaxillary lymph node LPS-induced proliferation. Cyclosporine decreased the high circulating prolactin levels found in pituitary-grafted rats. The results are compatible with age-dependent, inhibitory and promoting activities of hyperprolactinemia on immune responses in lymph nodes, affected in a complex antagonistic and synergistic way by cyclosporine immunosuppression.

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Section: Discussionmentioning

confidence: 81%

Effect of Cyclosporine on Immune Responses in Submaxillary Lymph Nodes of Pituitary-Grafted Rats

Arce

Castrillón²,

Della‐Maggiore³

et al. 1996

Neurosignals

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“…In particular, the augmentation of delayed-type hypersensitivity (DTH) skin reactions to ovalbumin (OVA) in guinea pigs from which CsA had been withdrawn following a short course of treatment has been reported [ 13]. More recent reports have confirmed that depending on the treatment regime, augmentation of immune reactivity can occur in CsA-treated animals [10], These findings clearly have important cautionary implications for the management of immunologically mediated dis eases of intermittent activity, such as certain autoim mune diseases and skin disorders where CsA might be applied [1]. Moreover, they indicate that the expres sion of DTH following CsA withdrawal (e.g.…”

Section: Introductionmentioning

confidence: 76%

Paradoxical Augmentation of Tuberculin-Like Hypersensitivity, but Not Jones-Mote or Contact Hypersensitivity, in Cyclosporin A Treated Guinea Pigs

Aldridge¹,

Thomson²

1986

Int Arch Allergy Immunol

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Administration of cyclosporin A (CsA; 25 mg/kg) orally to guinea pigs from the time of immunization with ovalbumin (OVA) in complete Freund’s adjuvant, followed by drug withdrawal 4 days later, resulted in marked potentiation of classical, tuberculin-like delayed-hypersensitivity skin responses to OVA. However, no such augmentation of delayed-type hypersensitivity (DTH) to purified protein derivative (PPD) was demonstrated. The enhancing effect of CsA was also dependent on the dose of OVA used for both immunization and skin testing and on the interval between drug withdrawal and the elicitation of DTH. A single intraperitoneal injection of CsA (200 mg/kg) given 2 days before immunization also had an augmentary effect on 14-day responses to OVA. Similar treatment protocols, however, did not enhance Jones-Mote (cutaneous basophil) hypersensitivity to OVA or contact sensitivity reactions to dinitrofluorobenzene. Longer courses of CsA (25 mg/kg per os) between sensitization and skin testing severely depressed all three categories of type IV hypersensitivity reactions. Our observations may have important cautionary implications for the prospective management of immunologically mediated diseases of intermittent activity, including certain autoimmune disorders, where short courses of CsA might be contemplated.

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“…Since adjuvant-induced arthritis is a Tlymphocyte-dependent autoimmune disorder [1][2][3], we tested the efficacy of immunosuppression by cyclosporine, a drug used to avert allograft rejection and in the therapy of autoimmune diseases [10][11][12], to counteract Freund's-adjuvant-induced changes in hormone release. Administration of cyclosporine restored the augmented ACTH and prolactin levels, and the depressed GH and TSH levels found in Freund's adjuvant-injected rats.…”

Section: Circadian Changes In Adenohypophysial Hormone Levels During mentioning

confidence: 99%

Circadian Rhythms in Adenohypophysial Hormone Levels and Hypothalamic Monoamine Turnover in Mycobacterial-Adjuvant-Injected Rats

Selgas

Pazo²,

Arce³

et al. 1998

Neurosignals

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The effect of Freund’s adjuvant injection on 24-hour variation in circulating ACTH, prolactin, growth hormone (GH) and thyroid-stimulating hormone (TSH) levels, and of hypothalamic norepinephrine (NE) content and dopamine (DA) and serotonin (5HT) turnover was examined in adult rats. In control rats, serum ACTH and prolactin exhibited peak values at the light-dark transition while the maximum in TSH was found in the late afternoon. GH levels did not vary on a 24-hour basis. In Freund’s-adjuvant-injected rats, 24-hour variations in TSH levels became blunted while 24-hour variations in prolactin and ACTH persisted. Freund’s adjuvant treatment augmented serum ACTH and prolactin levels, and decreased GH and TSH levels. Hypothalamic NE content, and turnover of DA and 5HT varied on a 24-hour basis in rats receiving adjuvant’s vehicle. The NE content of the anterior, medial and posterior hypothalamus peaked at 04.00 h, while that of the median eminence attained its maximum at 16.00–20.00 h. Maxima in hypothalamic DA and 5HT turnover occurred at 04.00 h regardless of the region examined. In Freund’s-adjuvant-injected rats, reduced amplitude of daily variations of NE content in the median eminence and anterior and medial hypothalamus, as well as a phase advance in the 24-hour rhythm of the posterior hypothalamic NE content were seen. Mycobacterial adjuvant injection also reduced the amplitude of circadian rhythm in hypothalamic 5HT turnover, shifted the maximum in median eminence DA turnover towards light-dark transition, and decreased the amplitude of DA turnover rhythm in the anterior, medial and posterior hypothalamus. Administration of the immunosuppressant drug cyclosporine restored the augmented ACTH and prolactin levels and the depressed GH and TSH levels found in Freund’s-adjuvant-injected rats. Cyclosporine was also effective to restore 24-hour rhythmicity of serum ACTH and TSH, but not of prolactin levels. Immunosuppression restored rhythmicity of NE content and of DA and 5HT turnover in anterior, medial and posterior hypothalamic regions. Cyclosporine did not modify the effect of Freund’s adjuvant on median eminence but in was able to counteract the changes in the DA and 5HT turnover in the median eminence found after immunization. The results are in accord with a significant effect of immune-mediated inflammatory response at an early phase after Freund’s adjuvant injection on ACTH, GH, prolactin and TSH release mechanisms, which was partially sensitive to immunosuppression induced by cyclosporine.

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Kinetics of the effect of a single dose of cyclosporin-A on antibody and cell mediated immune responses in the guinea pig

Cited by 22 publications

References 8 publications

Effect of Cyclosporine on Immune Responses in Submaxillary Lymph Nodes of Pituitary-Grafted Rats

Effect of Cyclosporine on Immune Responses in Submaxillary Lymph Nodes of Pituitary-Grafted Rats

Paradoxical Augmentation of Tuberculin-Like Hypersensitivity, but Not Jones-Mote or Contact Hypersensitivity, in Cyclosporin A Treated Guinea Pigs

Circadian Rhythms in Adenohypophysial Hormone Levels and Hypothalamic Monoamine Turnover in Mycobacterial-Adjuvant-Injected Rats

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