Eosinophilia with Aberrant T Cells and Elevated Serum Levels of Interleukin-2 and Interleukin-15

Abstract

HE hypereosinophilic syndrome comprises various idiopathic myeloproliferative disorders with sustained eosinophilia and damage to the heart, lungs, skin, and other organs by infiltrating eosinophils. 1 A single mechanism for this syndrome has not been identified, and multiple factors are likely to be involved. The serum level of interleukin-5, an eosinophilopoietic cytokine, is increased in some patients with the hypereosinophilic syndrome, 2 and a few have been found to have unusual T-cell abnormalities, including CD3¡CD4+CD8¡ T cells 3,4 and socalled double-negative CD3+CD4¡CD8¡ T cells. 5 CD3, a complex of five proteins associated with the T-cell receptor, is a distinctive feature of all normal T cells. CD4 and CD8 identify helper and cytotoxic T cells, respectively. Recently, Simon et al. described 16 patients with eosinophilia and unusual T cells, some of which secreted abnormal amounts of interleukin-5 when cultured in vitro. 6 The serum levels of interleukin-5 were not reported.We describe a patient with the hypereosinophilic syndrome who presented with a pericardial effusion, endobronchial lesions, and a population of activated T cells that expressed markers of natural killer cells (CD16 and CD56). Serum levels of interleukin-2 and interleukin-15, which are potent stimulators of the proliferation of T cells and natural killer cells, were elevated. After the initiation of therapy with hydroxyurea, the patient's condition improved markedly and the immunologic abnormalities resolved. CASE REPORTA 34-year-old man was referred to the pulmonary clinic at the National Naval Medical Center in April 1997 after nine months T of worsening cough with dyspnea. He had no personal or family history of asthma, atopy, or serious illnesses. He had received antibiotics intermittently and short courses of oral glucocorticoids for presumed postinfectious bronchospasm, but he otherwise took no medications routinely and had never taken tryptophan or any type of antileukotriene therapy. He had no known drug allergies and did not smoke. A complete blood count obtained during a routine examination in 1989 showed an elevated absolute eosinophil count of 770 per cubic millimeter (normal value, <450). This measurement was not repeated until his presentation in 1997.The physical examination revealed a pulse of 115 beats per minute and diffuse wheezing in both lungs. There were no skin lesions or organomegaly, and the neurologic examination was normal. Initial laboratory studies were remarkable only for the presence of eosinophilia (23 percent eosinophils; absolute eosinophil count, 2074 per cubic millimeter). The serum IgE level was normal. A chest radiograph revealed an enlarged cardiac silhouette but no parenchymal abnormalities. Echocardiography demonstrated a large pericardial effusion.Pericardiocentesis yielded 600 ml of exudate, with 44 percent eosinophils, 6 percent neutrophils, and 50 percent monocytes. The eosinophils appeared to be morphologically mature. Drainage of the pericardial fluid transiently relieved the orthopnea, ...

Interleukin 15: biology and relevance to human disease

“…223 This patient had elevated serum levels of IL-15 (13.8-36 pg/mL) and IL-2 (1160 pg/mL), and a major T-cell population expressing activation (CD25) and NK cell (CD16, CD56) markers was identified. Although treatment of the patient with steroids failed, the hypereosinophilia and symptoms resolved after hydroxyurea therapy, along with disappearance of the T-cell population and serum IL-15 and IL-2.…”

“…IL-15 and IL-2 may therefore have a role in the genesis of idiopathic eosinophilia and T-cell expansion, and the shared IL-2/15R␤ may be a useful target in such cases. 223 …”

Decreased IL-15 May Contribute to Elevated IgE and Acute Inflammation in Atopic Dermatitis

“…Commercial ELISA kits were used to determine the levels of IL-15 (R&D Systems) and IFN-␥ (Endogen, Woburn, MA). The IL-15 ELISA had a detection limit of Ͻ1 pg/ml (20), whereas the IFN-␥ ELISA had a detection limit Ͻ2 pg/ml.…”

Modern Diagnosis and Treatment of Primary Eosinophilia

“…Additional blood studies that are currently considered during the evaluation of primary eosinophilia include serum tryptase (an increased level suggests SM and warrants molecular studies to detect FIP1L1-PDGFRA ) [12, 34], T-cell immunophenotyping as well as T-cell receptor antigen gene rearrangement analysis (a positive test suggests an underlying clonal or phenotypically abnormal T-cell disorder and warrants measurement of IL-5 as well as consideration of T-cell-directed therapy) [24, 26], serum IL-5 (an elevated level requires careful evaluation of the bone marrow as well as the T-cell gene rearrangement studies for the presence of a clonal T-cell disease) [24], and serum IgE level (patients with increased IgE level might be at a lower risk of developing eosinophilia-associated heart disease) [35]. Furthermore, one must be alert about an HES phenotype with episodic angioedema, urticaria, fever, weight gain, and elevated levels of serum IgE, IgM, and polyclonal γ-globulins that is associated with a relatively benign, corticosteroid-responsive disease (Gleich syndrome) [36].…”

“…On the other hand, a small proportion of patient with HES manifest detectable clonal Th-2 lymphocytes and this might represent secondary, interleukin-5-mediated eosinophilia [24, 25]. A similar process is conceivable in HES associated with phenotypically abnormal but polyclonal T cells [26]. …”