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A Mixture of Nucleosides and Nucleotides Increases Bone Marrow Cell and Peripheral Neutrophil Number in Mice Infected with Methicillin-Resistant Staphylococcus aureus¹

Yoko Matsumoto, Andrew A. Adjei^*, Keiko Yamauchi, Mitsuo Kise, Yoko Nakasone, Yoshiyuki Shinagawa, Hiroomi Yokoyama and Shigeru Yamamoto²

Department of Nutrition and Research Center of Comprehensive Medicine ^* Department of Bacteriology Faculty of Medicine, University of the Ryukyus, Nishihara, Okinawa 903-03, Japan Otsuka Pharmaceutical Factory, Inc., Naruto, Tokushima, Japan

We studied the effects of a mixture of nucleosides and nucleotides on the peripheral neutrophil number and the proliferation of bone marrow cells in mice challenged with methicillin-resistant Staphylococcus aureus. BALB/c mice were fed a nucleotide-free 20% casein diet (control) or this diet supplemented with nucleosides and nucleotides orally (Expt. 1) or intraperitoneally (Expt. 2 and 3). On d 10, the mice were challenged intravenously with methicillin-resistant S. aureus (6.7 x 10¹² colony forming units/L). In Expt. 1 and 2, numbers of total and differential counts of blood leucocytes were counted on d 0 (before), 1, 3 and 5 after the infection. In Expt. 3, 30 min before killing, bromodeoxyuridine (20 mg/kg), an analogue of thymidine, was administered intraperitoneally and its incorporation in the DNA synthetic phase of bone marrow cells was determined at 0 h (before), 3, 6 and 24 h after the infection. Mice fed the supplemented diet had higher (P < 0.05) leucocyte and neutrophil numbers on d 0 compared with the control group. The neutrophil numbers tended to be greater in the supplemented group at 1, 3 and 5 d after the infection. Intraperitoneal administration of nucleosides and nucleotides increased (P < 0.05) neutrophil numbers before and after the infection. Twenty-four h after the infection, incorporation of bromodeoxyuridine into the DNA synthetic phase of bone marrow cells in the group administered nucleosides and nucleotides was higher (P < 0.05) than in the control group. We conclude that, following methicillin-resistant S. aureus injection, intraperitoneal administration of a nucleoside-nucleotide mixture may stimulate bone marrow cell proliferation and increase the peripheral blood neutrophil numbers. Oral administration may elicit weaker effects.

KEY WORDS: • nucleosides • nucleotides • neutrophils • hemopoiesis • mice

¹ 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.

² To whom correspondence should be addressed.

Manuscript received 7 March 1994. Revision accepted 21 September 1994.