Carica papaya increases regulatory T cells and reduces IFN-c 1 CD4 1 T cells in healthy human subjects Maha Abdullah 1,2 , Pei-Shin Chai 1 , Chiew-Yee Loh 1 , Mun-Yee Chong 1 , Huai-Wei Quay 1 , Sharmili Vidyadaran 1 , Zainina Seman 3 , Mirnalini Kandiah 4 and Heng-Fong Seow 1 1 Immunology Unit, Department of Pathology, Faculty of Medicine and Health Sciences (FMHS), Universiti Putra Malaysia (UPM), Malaysia 2 MAKNA-Cancer Research Laboratory, Institute of Biosciences, UPM, Malaysia 3 Hematology Unit, Department of Pathology, FMHS, UPM, Malaysia 4 Department of Nutrition and Dietetics, FMHS, UPM, Malaysia Received: February 10, 2011 Revised: February 10, 2011 Accepted: February 18, 2011 Fruit and vegetables have therapeutic potential as they dampen inflammation, have no known side-effects and as whole foods have prospective additive and synergistic benefits. Th1 (IFN-g 1 CD4 1 )/Th2 (IL-4 1 CD4 1 ) T cells play a vital role in mediating inflammatory responses and may be regulated by regulatory T cells (Tregs). Effects of Carica papaya on cells of healthy individuals were determined using flow cytometry methods. Significant down- regulation of IFN-g 1 CD4 1 (p 5 0.03, n 5 13), up-regulation of IL-4 1 CD4 1 (p 5 0.04, n 5 13) T cells and up-regulation of CD3 1 CD4 1 CD25 1 CD127 À (p 5 0.001, n 5 15) Tregs were observed after papaya consumption. In vitro cultures showed up-regulation of Tregs in male subjects and was significantly associated with levels of IL-1b in culture supernatants (R 2 5 0.608, p 5 0.04, n 5 12). Other inflammatory cytokines were significantly suppressed. Papaya consumption may exert an anti-inflammatory response mediated through Tregs and have potential in alleviating inflammatory conditions. Keywords: Carica papaya / Cytokines / Immunoregulation / Inflammation / Regulatory T cells Fruit and vegetables produce phytochemicals such as flavonoids and antioxidants, which modify the immune system [1] and lower markers of inflammation and oxidative stress [2], reducing risk of chronic diseases such as cancer and cardiovascular disease [3]. They have potential to improve conditions in autoimmune and transplantation diseases as phytochemicals suppress T-lymphocyte prolif- eration in vitro and in vivo [4]. Flavonoid such as naringenin [5], green tea polyphenol extract [6], encapsulated fruit and vegetable juice powder concentrate [7] were shown to reduce levels of inflammatory cytokines. Papaya (Carica papaya Linn) is low in calories, high in vitamins, minerals and a rich source of enzymes [8]. Its rich content of ascorbic acid provide anti-oxidative protection [9] and its shoot exhibit high levels of flavonoids such as quercenin and kaempferol [10]. Papaya is also appreciated worldwide for its flavour, nutritional qualities and digestive properties and valued for its medicinal and pharmacological properties including immunomodulatory potentials [8]. Regulatory T cells (Tregs) maintain homeostasis of the immune system and suppress immune responses of a wide range of immune cells, including T cells, natural killer and B cells. Their dysfunction causes fatal autoimmune disease, immunopathology and allergy [11]. Deficiencies in Tregs may also be linked with infertility, miscarriage and pre-eclampsia [12]. The potential role of Tregs in the resolution of diseases in which IFN-g Th1 1 cells play a pathologic function is recognized [13]. The involvement of Tregs in the immunomodulatory effect of fruits and vege- table has not been studied. We examined the effect of papaya on Th1, Th2, Tregs and inflammatory cytokines in healthy human. FOOD &FUNCTION Abbreviations: PBMC, peripheral blood mononuclear cell; TNF, tumor necrosis factor; Treg, regulatory T cell Correspondence: Dr. Maha Abdullah, Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, UPM 43400, Serdang, Selangor, Malaysia E-mail: maha@medic.upm.edu.my Fax: 1603-89412787 & 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.mnf-journal.com Mol. Nutr. Food Res. 2011, 55, 803–806 803 DOI 10.1002/mnfr.201100087