Table 1 Summary of the research manuscripts assessing the role of H2-antagonist in IgE-mediated type I hypersensitivity reactions

Kupczyk et al. [8]

In vivo human study

Ranitidine

Ranitidine was able to suppress the wheal, flare, and itching sensation in SPT

Runge et al. [9]

In vivo human study

Cimetidine

Diphenhydramine

In acute urticaria, cimetidine + diphenhydramine is more effective than diphenhydramine alone.

Lin et al. [10]

In vivo human study

Ranitidine

Diphenhydramine

The addition of ranitidine to diphenhydramine results in improvement of cutaneous manifestations in patients with acute allergic syndromes

Dhanya et al. [11]

In vivo human study

Ranitidine

Levocetirizine

Levocetirizine + ranitidine resulted in significant reduction of wheal size at 2, 3, 6, and 24 h vs. levocetirizine alone.

Arias et al. [12]

In vivo mouse study

Cimetidine

Mepyramine

The co-administration of H₁- and H₂-antagonist had no impact on the severity or the course of anaphylactic reaction

Shah et al. [13]

In vivo human study

Famotidine

Ranitidine

Cimetidine

H₂-antagonists had no effect on the positive histamine skin test; if associated with other potentially antihistaminic medications, the odds of a negative histamine control increased. Authors concluded that a 0–2-day discontinuation before testing is recommended.

Fedorowicz et al. [14]

Review on human studies

Famotidine

Ranitidine

Cimetidine

Evidence for the effectiveness of H₂-antagonist in urticaria is limited, weak and unreliable. Based on the review, there is not enough evidence to answer the question of whether H₁- + H₂-antagonists are better than just H₁- antagonists alone.

Guevara-Gutierrez et al. [15]

In vivo human study

Ranitidine

Cetirizine

Combination therapy with cetirizine and ranitidine was not more effective than cetirizine alone in chronic urticaria.

Hatakeyama et al. [16]

In vivo human study

Lafutidine

Cetirizine

Fexofenadine

Bepotastine

Ebastine

Olopatadine

Levocetirizine

Authors concluded that lafutidine can be recommended as an adjunct therapy that improved disease activity and QoL in patients with refractory cholinergic urticaria.

Ogawa et al. [17]

In vivo human study

Lafutidine

H₁-antagonists (not specified)

In idiopathic chronic urticaria, lafutidine as adjuvant therapy showed a moderate improvement or better in 85 and 76 % of patients after 1– 3 weeks and after 3 months, respectively. Lafutidine was rated as useful or better in 74 % of evaluated patients after 3 months of treatment.

Zhang et al. [19]

In vitro human study

Cimetidine

Cimetidine suppresses the function of Treg cells through a reduction of Foxp3 via E3 ligase Stub1-mediated proteosomal degradation.

Avella et al. [20]

In vivo human study

Cimetidine

Cimetidine therapy prevented a natural decline in delayed hypersensitivity skin tests to four common antigens and significantly increased delayed hypersensitivity, measured by the degree of erythema at both 24 and 48 h and induration at 48 h.

Arae et al. [21]

In vivo, in vitro mouse model

Cimetidine

Administration of cimetidine to Ovalbumin-sensitized BALB/c mice increased serum level of Ovalbumin-specific IgE, IgG₁ and IgG_2a. In vitro analysis showed an increased IL-5 secretion by Ovalbumin-stimulated spleen cells.

Shin et al. [22]

In vivo mouse model

Ranitidine

Treatment with ovalbumin immunotherapy + ranitidine showed a significant increase in serum specific IgE levels, nasal lavage fluid IL-13 levels and the number of tissue eosinophils when compared both with immunotherapy alone and with immunotherapy + H₂-agonist.

Ishikura et al. [23]

In vivo human study

Cimetidine

Cimetidine significantly increases serum IL-12 levels in patient admitted to the intensive care unit

Hahm et al. [24]

In vitro human study

Cimetidine Ranitidine

Famotidine

In peripheral blood mononuclear cells from patients with gastric cancer, cimetidine increases the cytotoxicity and proliferative response of lymphocyte to mitogen

Jafarzadeh et al. [25]

In vivo mouse model

Cimetidine

In a mouse model, cimetidine significantly increased both serum levels of IL-2, IL-10, IL-12, and IL-17 and delayed type hypersensitivity responses that are normally suppressed after a burn injury.

Pastorello et al. [26]

In vivo human study

H₂-antagonists (not specified)

Therapy with H₂-antagonists was significantly associated with an increase in the risk of a severe reaction to amoxicillin. Patients that had received H₂-antagonists presented higher levels of specific IgE.

van der Pouw Kraan et al. [27]

In vitro human study

Ranitidine

In human monocytes, ranitidine reversed the inhibition of IL-12 production caused by histamine.

Lee et al. [30]

In vivo, in vitro, human and mouse model

Roxatidine

Roxatidine suppressed both the expression of TNF-α, IL-6, and IL-1β, and the activation of caspase-1, in stimulated human mast cells and in anaphylactic mouse model. In animal model of allergen-induced contact hypersensitivity, roxatidine significantly reduced ear swelling, mast cell accumulation, cytokine levels, and dendritic cell migration in sections of ear tissue.

Geng et al [31]

In vivo human study

H₂-antagonists (not specified)

The administration of H₂-antagonists is associated with a significant odds ratio for a negative histamine response at prick test.

Simons et al. [32]

In vivo human study

Cimetidine

Hydroxyzine

Hydroxyzine + cimetidine showed a significant increase both in serum hydroxyzine concentrations and in suppression of the histamine-induced wheal and flare.