Inflamm. res. 55 (2006) 354–358 1023-3830/06/080354-5 DOI 10.1007/s00011-006-6044-8 Inflammation Research © Birkhäuser Verlag, Basel, 2006 The effects of fructose-1,6-bisphosphate and dexamethasone on acute inflammation and T-cell proliferation R. Pestana Lopes 1 , A. Lunardelli 2 , T. Preissler 1 , C. E. Leite 2 , J. C. F. Alves-Filho 4 , F. Bordignon Nunes 2,3 , J. Rodrigues de Oliveira 2,3 and M. E. Bauer 1,3 1 Laboratory of Cellular and Molecular Immunology, Institute of Biomedical Research, Hospital São Lucas, PUCRS, Av. Ipiranga 6690, 2 andar – Caixa Postal 1429. 90.610-000 Porto Alegre, RS. Brazil, Fax: ++55 51 33203312, e-mail: mebauer@pucrs.br 2 Laboratory of Biophysics 3 Faculty of Biosciences, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Av. Ipiranga, 6681, 12C, PO Box 1429, Porto Alegre, RS, Brazil 4 Department of Pharmacology, University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, SP, Brazil Received 7 November 2005; returned for revision 15 January 2006; accepted by I. Ahnfelt-Rønne 29 March 2006 Abstract. Objective and design: Chronic glucocorticoid treatment is associated with pharmacological resistance. We investigated the auxiliary effects of fructose-1,6-bisphos- phate (FBP) on dexamethasone (DEX)-related modulation of inflammation and T-cell proliferation. Methods: Acute inflammation (pleurisy) was induced by in- jection of carrageenan into the pleural cavity of rats that were treated in vivo with DEX s. c. and FBP i. p. Peripheral blood mononuclear cells were isolated and T-cell sensitivity to FBP and DEX was evaluated in vitro. Results: FBP and DEX reduced the exudate volume, protein concentration and neutrophils in the pleural cavity. However no synergistic effects were observed when these compounds were tested simultaneously. In contrast, both compounds dose-dependently and synergistically suppressed T-cell pro- liferation. Conclusion: These data suggest that FBP may be beneficial as auxiliary drug for the treatment of patients with acquired glucocorticoid resistance. Key words: Inflammation – Glucocorticoids – Fructose-1,6- bisphosphate – Human T-lymphocytes – Pleurisy Introduction Fructose-1,6-bisphosphate (FBP) is a high-energy interme- diate metabolite of glycolysis [1] with reported therapeutic effects not shared by other phosphorylated sugars [2]. Sev- eral studies have described FBP’s action in reducing tissue damage associated with ischemia [3, 4], shock [5, 6] and toxic injury [7, 8]. We and others have previously shown that FBP significantly reduced the mortality rate provoked by experimental sepsis [9], suppressed rat paw edema [10, 11] and protected against carrageenan induced pleurisy [12]. Furthermore, FBP’s suppressive effects on T-cell prolifera- tion have also been described in both human [13] as well as rodent [10] peripheral cells. However, the auxiliary FBP ef- fects on glucocorticoid-induced suppression of inflammation are largely obscure. Synthetic glucocorticoids (GCs), including dexametha- sone (DEX), have been widely used as antiinflammatory and immunosuppressive drugs in the treatment of several inflammatory diseases including rheumatoid arthritis, sys- temic lupus erythematosus (SLE) and allergies [14]. GCs act through specific binding in two distinct intracellular and membrane receptor subtypes: the mineralocorticoid (MR) and glucocorticoid receptors (GR). After being bound, the receptor-ligand complex translocates to the nucleus, where it either binds to glucocorticoid response elements (GREs) on DNA or interacts with other transcription factors in order to regulate gene expression [15]. Physiological and metabolic alterations promoted by chronic and/or abusive corticosteroid therapy may lead to the development of several adverse reactions such as ster- oid-induced osteoporosis [16, 17], diabetes mellitus [18, 19], psychiatric and cognitive disorders [20], endocrine com- plications [21, 22], as well as pharmacological resistance [23–25]. Therefore, the search for compounds with auxiliary anti-inflammatory and immunosuppressive effects may be of valuable clinical significance. Here, we describe both the anti-inflammatory and immunosuppressive FBP effects on DEX-related immunomodulatory actions. In particular, we evaluated the synergistic (i) in vivo DEX and FBP anti-in- flammatory effects on carrageenan-induced pleurisy in rats as well as (ii) in vitro effects of these compounds in sup- pressing human T-cell proliferation. Correspondence to: M. E. Bauer