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Energy Restriction Prevents and Reverses Immune Thrombocytopenic Purpura (ITP) and Increases Life Span of ITP-Prone (NZW x BXSB) F₁ Mice^1,2,

Hajime Mizutani, Robert W. Engelman³, Yoshiyuki Kurata^*, Susumu Ikehara and Robert A. Good

Department of Pediatrics, University of South Florida, All Children's Hospital, St. Petersburg, FL 33701 ^* Department of Blood Transfusion, Osaka University Hospital, Osaka 565, Japan First Department of Pathology, Kansal Medical University, Osaka 560, Japan

Male (NZW x BXSB)F₁ (W/BF₁) mice develop immune thrombocytopenic purpura (ITP), which involves antiplatelet autoantibodies and shortened platelet life span. To determine whether reduction of dietary energy can prevent the development or reverse the progression of ITP, male W/BF₁ mice were separated into five experimental groups and either given free access to semipurified diet (designated Group A, n = 50) or consumed 32% less energy from an otherwise comparable diet (Group B₆, n = 20), or were initially allowed free access to diet then switched to energy restriction at ages 14, 17 or 22 wk (Groups B₁₄, n = 10; B₁₇, n = 20; B₂₂, n = 20). Thrombocytopenia was prevented by energy restriction in Group B₆ mice. Platelet-associated IgG (PAIgG) autoantibody levels and the number of splenic antiplatelet antibody-forming cells were low (P < 0.01) and the survival of injected IgG-coated RBC was extended in energy-restricted Group B₆ mice (P < 0.01) compared with mice in Group A. Group A mice became progressively thrombocytopenic, with platelet counts as low as 34 x 10¹⁰/L. Progression of thrombocytopenia was reversed when energy restriction was initiated in Groups B₁₄, B₁₇ and B₂₂, with platelet counts 88 x 10¹⁰/L and reduction of PAIgG. Life span was extended among early onset energy-restricted Group B₆ and Group B₁₄ mice (P = 0.0001 and P = 0.005) but not among late onset energy-restricted Group B₁₇ and Group B₂₂ mice (P = 0.06 and P = 0.35) compared with Group A mice. These data suggest that dietary adjuncts to conventional therapies should be considered in the management of ITP patients.

KEY WORDS: • platelets • autoimmunity • mice • energy restriction • immune thrombocytopenic purpura

¹ Supported by grants from the Eleanor Naylor Dana Charitable Trust, National Institutes of Health (AG05633 and CA41061), Suncoast Cardiovascular Research and Education Foundation, Newland Foundation, and Ronald McDonald Charities.

² The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

³ To whom correspondence should be addressed.

Manuscript received 14 February 1994. Revision accepted 18 April 1994.