Streptozocin Introduction br Chronic inflammation state and

Introduction
Chronic Streptozocin state and MPN: Results from epidemiology Phenomena of autoimmune myelofibrosis or PMF presenting autoimmune phenomena have been reported [24], [25], [26]. A large population-based study including 11039 MPN patients and 43550 matched controls showed that 2.6% MPN patients had a previous history of autoimmune problems such as immune thrombocytopenic purpura (ITP), Crohn’s disease (CD), polymyalgia rheumatica (PMR), giant cell arteritis, Reiter’s syndrome and aplastic anemia. Patients with a history of these autoimmune problems presented an increased risk of developing MPN [27]. More recently in 2011, results from a systematic review of a literature search indicated that autoimmune conditions are associated with the development of myeloid neoplasms including MPNs. In particular, CD was found to be associated with the occurrence of MPN, and JAK2 mutations were also identified in CD patients [28]. One recent case study with 323 MPN patients and 333 chronic lymphocytic leukemia (CLL) patients demonstrated an increased risk of MPN in populations with a history of autoimmune disease. Interestingly, this study showed JAK2-positive MPN patients presented a higher incidence of prior ischemic disease and thromboembolic events compared to JAK2-negative MPN patients [29]. It has been established that autoimmune disease is essentially chronic inflammation disease and that vascular problems are due to persistent chronic inflammation; we, therefore, suggest that there is a link between MPN and chronic inflammation. Furthermore, we speculate that persistent chronic inflammation could more likely be due to gene mutation, which results in JAK2-positive MPN.
Cytokine profile in MPN: Results from experimental investigation Cytokines are small molecules constituted by proteins or glycoproteins, which regulate the immune cell function and the immune system. They are secreted mainly by immune cells but also by other cells such as epithelial cells in response to all kinds of stimulation such as injury, infection and stress. They are considered mediators of inflammation and play critical roles in acute and chronic inflammation. In addition to the classically defined cytokines such as interleukins (ILs) and interferons (IFNs), there are a variety of other factors including tumor necrosis factors (TNFs), chemokines, colony stimulating factors (CSF), cell growth factors (TGF, HGF, PDGF and FGF), and angiogenic factors (such as VEGF) [30], [31]. The major immunomodulatory role of cytokines is the recruitment of immune effector cells to eradicate invasive stimuli. This process comprises transmission and feedback of information between the immune cell producing center and exertion of local activities that include angiogenesis, cell proliferation and cell migration. A balance in the cytokine network between pro-inflammatory and anti-inflammatory effects is required for effectively controlling normal function. Otherwise, its dysregulation could generate organ disorders or even diseases. Dysregulation of cytokine networks has been reported in MPN [21]. Cytokines evaluated in 15 MPN studies (literature from 1997 to 2018) are summarized in Table 1.