The purpose of this study is to evaluate the anti-inflammatory properties of JNJ-26528398 using an intravenous (IV) endotoxin-induced model of acute, transient inflammation.

This is a 2-part, single center, double-blind study (neither physician nor participant knows the treatment that the participant receives). Part 1 is designed to evaluate the safety, tolerability, and pharmacokinetics (level of drug in the blood) of a dosing regimen of an investigational drug (JNJ-26528398) prior to its use in Part 2. In Part 1, participants will be assigned by chance to receive either 3 mg/day JNJ-26528398 (6 participants) or placebo (3 participants) for 7 consecutive days while staying in the clinic for 10 days. Placebo is an inactive substance that is compared with a drug to test whether the drug has a real effect. Part 2 is designed to evaluate the anti-inflammatory properties of JNJ-26528398 by measuring markers of inflammation in the blood after intravenous (IV) administration of a substance (endotoxin) which activates the immune system and temporarily causes flu-like symptoms. In Part 2, participants will be assigned by chance to receive up to 3 mg/day JNJ-26528398 (6 participants) or placebo (4 participants) for up to 7 consecutive days while staying in the clinic for 10 days. Endotoxin will be given on the last day of study drug administration. Participants will remain in bed for at least 6 hours after endotoxin administration and will be closely monitored by study personnel.

Inclusion Criteria:

• Nonsmoker
• Be in good health on the basis of physical examination, medical history, and electrocardiogram (ECG)
• Must have good exercise tolerance
• Have a body mass index of 18-29 kg/m2, inclusive, and body weight between 60 and 85 kg, inclusive
• Have a history of consistent dental hygiene and dental care
• Must adhere to required contraception (subject and partner, if applicable) during the study and for 3 months after study
• Must agree to not donate sperm during the study and for 3 months after study

Exclusion Criteria:

• Is currently enrolled in an investigational study, has recently received an investigational drug (including investigational vaccines), or has donated blood within 3 months
• Has had a vaccination within past 3 months
• Has history of significant drug or alcohol abuse within past 2 years or has a positive drug screen
• Blood donation within past 3 months
• Part 2 only: Has received endotoxin within past 3 months, or has a known allergy or history of significant adverse reaction to endotoxin or its excipients lactose and polyethylene glycol 6000