First Time in Human Study of Intravenous Interleukin-18 Antibody

Inclusion Criteria: * Males aged 18-65 years inclusive at the time of signing informed consent. * Subjects must agree to use one of the contraception methods required. * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. * Available to complete all study assessments. * Able to read, comprehend and write English at a sufficient level to complete study related materials. * Healthy as determined by a responsible and experienced physician. * Positive delayed type hypersensitivity (DTH) reaction to candida antigen within 72 hrs of screening visit (group 4, 8 and 9 subjects only in Part 1). * Body weight equal or greater than 50kg and BMI within the range of 19-29.9kg/m2 (Part 1 only). * BMI within the range 30 - 40kg/m2 (Part 2 only). * Waist circumference \>102cm (Part 2 only). * Fasting plasma insulin \>60pmol/L (Part 2 only). Exclusion Criteria: * A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening. * A positive pre-study drug/alcohol screen. * A positive test for HIV antibody. * A positive test for influenza A/B. * A positive test for Mycobacterium tuberculosis. * History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of \>21 units or average daily intake of \>3 units. One unit is equivalent to 8 g of alcohol, and the following can be used as a guide: a half-pint (\~240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits. * The subject is unwilling to abstain from alcohol consumption from 24 hr prior to dosing until discharge from the clinic, and for 24 hr prior to all other out-patient clinic visits. * The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 90 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). * Exposure to more than four new chemical entities within 12 months prior to the first dosing day. * Subject has received live, attenuated or recombinant vaccine(s) within 2 months of randomisation or will require vaccination prior to the time at which plasma levels are predicted to reach an average level of approximately 1.0 µg/mL from when the dose is administered or Day 56 whichever is longer. * Current evidence, or history within the last 7 days, of an influenza-like illness as defined by fever (\>38°C) and two or more of the following symptoms: cough, sore throat, runny nose, sneezing, limb / joint pain, headache, vomiting / diarrhoea in the absence of a known cause, other than influenza. * Use of anti-Tumor Necrosis Factor (anti-TNF) or anti-Interleukin-1 (anti-IL-1) drugs within 60 days prior to dosing. * Current evidence of ongoing or acute infection, history of repeated, chronic or opportunistic infections (e.g. recurrent folliculitis, other cutaneous infections or repeated pneumonia) or history of a serious bacterial infection within 6 months of randomisation. * History of significant cardiac, pulmonary, metabolic, renal, hepatic, or gastrointestinal conditions that in the opinion of the study physician and/or GSK physician, places the subject at an unacceptable risk as participant in this trial. * History of Mycobacterium tuberculosis or any other previous Mycobacterium infection. * Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the study physician and GSK physician the medication will not interfere with the study procedures or compromise subject safety. * History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the study physician or GSK physician contraindicates their participation. * Current chronic (greater than 3 months) treatment with prescription anti-inflammatory drugs, including corticosteroids and non-steroidal anti-inflammatory drugs. * History of a severe allergic reaction, angio-edema, anaphylaxis or immunodeficiency. * History of malignancy, except for adequately treated non-invasive cancer of the skin (basal or squamous cell) (\> 2 yrs prior to dosing). * Subject whose calculated creatinine clearance is less than 80 mL/min * Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period. * Subject is unable to refrain from travelling to countries with a high prevalence of infectious disease from when the dose is administered until the time at which the plasma concentration of GSK1070806 is predicted on average to be approximately 1.0µg/mL from when the dose is administered or Day 56 whichever is longer. * Unwillingness or inability to follow the procedures outlined in the protocol. * Subject is mentally or legally incapacitated. * Liver function tests above the upper limit of normal at screening (alkaline transaminase (ALT), aspartate transaminase (AST) or bilirubin) (Part 1 subjects only). * Liver function tests above 2 x the upper limit of normal at screening (alkaline transaminase (ALT), aspartate transaminase (AST)) or 1.5 x the upper limit of normal (bilirubin) (Part 2 subjects only). * Corrected QT interval (QTc) \> 450 msec. * Subjects who have asthma or a history of asthma, COPD or pneumonia (Note: a subject who suffered from childhood asthma but not as an adult may be included provided they fulfil other entry criteria.) * Subject has had symptomatic herpes zoster infection within 3 months of randomisation. * Subjects with a smoking history of \>10 cigarettes per day in the last 3 months. * Experiencing clinically significant ECG abnormalities at screening or at baseline. * History of elevated blood pressure or current systolic blood pressure \> 140mmHg or diastolic blood pressure \>90mmHg. (Part 1 only). * Has a fasting plasma glucose value equal or greater than 7 mmol/L at screening or at baseline, or has been diagnosed with Type 1 or Type 2 diabetes mellitus (Part 2 only) * Has a fasting triglyceride level \>4.52 mmol/L at screening or at baseline. Triglyceride levels within a 5-10% margin above this level will be considered on a case-by-case basis (Part 2 only). * Subjects currently receiving weight loss treatment such as, but not limited to: "crash"/starvation diets (e.g. \<800ckal/day), ALLI™ (Orlistat), Ephedra (ma-huang) or other ephedrine based treatments, Cascara or other herbal treatments which, in the opinion of the investigator and/or GSK Medical Monitor, contraindicates the subject's participation. Subjects must not participate in any of the weight loss treatment outlined above during the course of the study (Part 2 only). * Subjects planning a substantial change to their diet during the course of the study (Part 2 only). * Subjects who have participated in a weight loss treatment outlined above within 4 weeks of randomisation (Part 2 only). * Systolic blood pressure \> 150mmHg or diastolic blood pressure \> 90mmHg at screening (Part 2 only).