Please cite this article in press as: Perac ¸ oli, J.C., et al., High levels of heat shock protein 70 are associated with pro-inflammatory cytokines and may differentiate early- from late-onset preeclampsia. J. Reprod. Immunol. (2013), http://dx.doi.org/10.1016/j.jri.2013.08.003 ARTICLE IN PRESS G Model JRI-2216; No. of Pages 6 Journal of Reproductive Immunology xxx (2013) xxx–xxx Contents lists available at ScienceDirect Journal of Reproductive Immunology j o ur na l ho me pag e: www.elsevier.com/locate/ jreprimm High levels of heat shock protein 70 are associated with pro-inflammatory cytokines and may differentiate early- from late-onset preeclampsia Jose C. Perac ¸ oli a , Camila F. Bannwart-Castro a , Mariana Romao b , Ingrid C. Weel b , Vanessa R. Ribeiro b , Vera T.M. Borges a , Marilza V. Rudge a , Steven S. Witkin c , Maria T. Perac ¸ oli b,∗ a Department of Obstetrics and Gynecology, Botucatu Medical School, UNESP – Sao Paulo State University, Botucatu, Sao Paulo, Brazil b Department of Microbiology and Immunology, Institute of Biosciences, UNESP – Sao Paulo State University, Botucatu, Sao Paulo, Brazil c Department of Obstetrics and Gynecology, Division of Immunology and Infectious Diseases, Weill Cornell Medical College, New York, NY, USA a r t i c l e i n f o Article history: Received 7 March 2013 Received in revised form 8 July 2013 Accepted 7 August 2013 Keywords: Cytokines Hsp60 Hsp70 Preeclampsia IUGR a b s t r a c t Preeclampsia (PE), a specific syndrome of pregnancy, can be classified into early and late onset, depending on whether clinical manifestations occur before or after 34 weeks’ gestation. We determined whether plasma concentrations of Hsp60 and Hsp70 were related to circulating cytokine levels, as well as kidney and liver functions, in early- and late-onset PE. Two hundred and thirty-seven preeclamptic women (95 with early- and 142 with late-onset PE) were evaluated. Plasma levels of Hsp60, Hsp70, and their specific antibodies, tumor necrosis factor-alpha (TNF-), interleukin (IL)-1, IL-10, IL-12, and soluble TNF--receptor I (sTNFRI) concentrations, were determined by enzyme- linked immunosorbent assay (ELISA). Concentrations of Hsp70, TNF-, IL-1, IL-12, and sTNFRI were significantly elevated in patients with early-onset PE compared with women with late-onset PE; IL-10 levels were significantly lower in the early-onset PE group. Concentrations of urea, uric acid, proteinuria, glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and lactate dehydrogenase (LDH) were also sig- nificantly higher in early-onset PE. The percentage of infants with intrauterine growth restriction was also significantly higher in women with early-onset PE. There were pos- itive correlations between Hsp70 levels and TNF-, TNFRI, IL-1, IL-12, GOT, GPT, LDH, and uric acid concentrations in early-onset PE group. Thus, early-onset PE was associated with greater maternal and fetal impairment. There are differences in pathophysiol- ogy between early- and late-onset PE, highlighting by the difference in Hsp70 levels. © 2013 Elsevier Ireland Ltd. All rights reserved. ∗ Corresponding author at: Department of Microbiology and Immunol- ogy, Institute of Biosciences, UNESP – Sao Paulo State University, Botucatu, Sao Paulo CEP 18618-970, Brazil. Tel.: +55 14 3880 1015; fax: +55 14 38153744. E-mail address: peracoli@ibb.unesp.br (M.T. Perac ¸ oli). 1. Introduction Preeclampsia (PE) affects between 5% and 7% of preg- nant women (Unal et al., 2007) and is characterized by new-onset hypertension and proteinuria after 20 weeks’ gestation (Walker, 2000). Strong evidence suggests an association between PE and elevated levels of circu- lating proinflammatory cytokines and oxidative stress. The subsequent triggering of endothelial dysfunction 0165-0378/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jri.2013.08.003