Phosphodiesterase inhibitors suppress proliferation of peripheral blood mononuclear cells and interleukin-4 and -5 secretion by human T-helper type 2 cells

Crocker, I.C.; Townley, Robert G.; Khan, Mohammad Saghir

doi:10.1016/0162-3109(95)00053-4

Cited by 54 publications

(23 citation statements)

References 29 publications

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“…Since the cytokine milieu at the time of initial allergen sensitization can determine the phenotype of the immune response to an allergen, alterations in this milieu by PTX could account for its effect on AHR. Although PDE 4-specific inhibitors have been shown to inhibit Th2 cytokine expression by Th2 cells and by PBMCs from atopic individuals, they have also been shown to inhibit Th1 cytokine production by Th1 cells in vitro and in animal models of Th1-mediated disease in vivo (63)(64)(65)(66)(67)(68)(69)(70)(71)(72). For the nonspecific PDE inhibitor PTX, data indicate that both in vitro and in vivo, in naive and differentiated cells, PTX inhibits Th1 cytokine production and has either no effect or an enhancing effect on Th2 cytokine production (18 -22, 24 -30).…”

Section: Discussionmentioning

confidence: 99%

Administration of Pentoxifylline During Allergen Sensitization Dissociates Pulmonary Allergic Inflammation from Airway Hyperresponsiveness

Fleming

Ciota

et al. 2001

The Journal of Immunology

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Asthma, a chronic inflammatory disease characterized by intermittent, reversible airflow obstruction and airway hyperresponsiveness (AHR), is classically characterized by an excess of Th2 cytokines (IL-13, IL-4) and depletion of Th1 cytokines (IFN-γ, IL-12). Recent studies indicating an important role for Th1 immunity in the development of AHR with allergic inflammation suggest that Th1/Th2 balance may be important in determining the association of AHR with allergic inflammation. We hypothesized that administration of pentoxifylline (PTX), a phosphodiesterase inhibitor known to inhibit Th1 cytokine production, during allergen (OVA) sensitization and challenge would lead to attenuation of AHR in a murine model of allergic pulmonary inflammation. We found that PTX treatment led to attenuation of AHR when administered at the time of allergen sensitization without affecting other hallmarks of pulmonary allergic inflammation. Attenuation of AHR with PTX treatment was found in the presence of elevated bronchoalveolar lavage fluid levels of the Th2 cytokine IL-13 and decreased levels of the Th1 cytokine IFN-γ. PTX treatment during allergen sensitization leads to a divergence of AHR and pulmonary inflammation following allergen challenge.

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Section: Discussionmentioning

confidence: 99%

Administration of Pentoxifylline During Allergen Sensitization Dissociates Pulmonary Allergic Inflammation from Airway Hyperresponsiveness

Fleming

Ciota

et al. 2001

The Journal of Immunology

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“…Other studies support a dichotomy in β 2 -AR effects on Th1 and Th2 cells, such that their activation modulates Th1 cell differentiation and cytokine production, but does not alter Th2 effector cells [131,197,203,198,[207][208][209]. Interestingly, increasing intracellular cAMP levels in Th2 cells can modulate IL-4 production [210][211][212][213]. Therefore, cAMP-mediated modulation of cytokine production by Th2 effector cells may depend on the manner in which the Th2 cells are activated or the level of cAMP attained intracellularly [190].…”

Section: Functional Significance Of Sympathetic Innervation Of Secondmentioning

confidence: 99%

Sympathetic modulation of immunity: Relevance to disease

Bellinger

Millar

Perez

et al. 2008

Cellular Immunology

223

185

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Optimal host defense against pathogens requires cross-talk between the nervous and immune systems. This paper reviews sympathetic-immune interaction, one major communication pathway, and its importance for health and disease. Sympathetic innervation of primary and secondary immune organs is described, as well as evidence for neurotransmission with cells of the immune system as targets. Most research thus far as focused on neural-immune modulation in secondary lymphoid organs, and have revealed complex sympathetic modulation resulting in both potentiation and inhibition of immune functions. SNS-immune interaction may enhance immune readiness during disease-or injury-induced 'fight' responses. Research also indicate that dysregulation of the SNS can significantly affect the progression of immune-mediated diseases. However, a better understanding of neural-immune interactions is needed to develop strategies for treatment of immune-mediated diseases that are designed to return homeostasis and restore normal functioning neural-immune networks.

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“…Theophylline inhibited proliferation of PBMC from atopic individuals, as well as IL-4 and IL-5 secretion from TH 2-like cells (21). However, theophylline did not inhibit stimulated release of IL-13 from PBMCs (22).…”

Section: Discussionmentioning

confidence: 99%

Theophylline as “Add-on” Therapy in Patients with Delayed Pressure Urticaria: A Prospective Self-Controlled Study

Kalogeromitros

Kempuraj

Katsarou-Katsari

et al. 2005

Int J Immunopathol Pharmacol

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Delayed pressure urticaria (DPU) is a skin condition that involves the gradual development of wheals and edema at sites of physical pressure. Its pathogenesis is not clear and histamine-1 receptor (H-1R) antagonists provide only partial relief. In this prospective, clinical study, we investigated the effect of theophylline, which has a long history of benefit in allergic asthma, added to cetirizine in patients with DPU. Twenty three patients received during period #1 cetirizine (10 mg po QD) and theophylline (200 mg po BID) for 6 months, followed by period #2 of 1 month washout with only rescue medication as needed, and then by period #3 with cetirizine (10 mg QD plus placebo (BID) for 5 more months. The addition of theophylline resulted in statistically significant improvement over cetirizine alone by 2 months and continued for the duration of treatment. Treatment of cultured human mast cells with theophylline (10 u M) did not inhibit allergic histamine release, but the in vivo beneficial effect of theophylline may require significant pretreatment period to manifest itself, or may involve inhibition of other mast cell dependent mediators. A double-blind study, accompanied by serum histamine and tryptase levels, should be in order.

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Phosphodiesterase inhibitors suppress proliferation of peripheral blood mononuclear cells and interleukin-4 and -5 secretion by human T-helper type 2 cells

Cited by 54 publications

References 29 publications

Administration of Pentoxifylline During Allergen Sensitization Dissociates Pulmonary Allergic Inflammation from Airway Hyperresponsiveness

Administration of Pentoxifylline During Allergen Sensitization Dissociates Pulmonary Allergic Inflammation from Airway Hyperresponsiveness

Sympathetic modulation of immunity: Relevance to disease

Theophylline as “Add-on” Therapy in Patients with Delayed Pressure Urticaria: A Prospective Self-Controlled Study

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