Mild-Intensity Whole Body Hyperthermia (WBH) for Major Depressive Disorder

Inclusion Criteria: 1. Ability to provide informed consent for study participation. 2. Males and females between the age of 18 and 65 years. 3. Have a current primary psychiatric diagnosis of major depressive disorder (MDD) of at least 4 weeks duration, as defined by DSM-5 criteria using the MINI v.7.0. 4. A Screening and Baseline visit Clinician-Administered Inventory of Depressive Symptomatology Questionnaire (IDS-C30) score ≥ 25. 5. Screening visit high-sensitivity C-reactive protein (CRP) concentration ≤ 5 mg/L (based on evidence that cytokine antagonism has an independent antidepressant effect in depressed patients with elevated CRP above this cut-off). Exclusion Criteria: 1. Any of the following medical conditions: * cardiovascular disease (other than controlled hypertension) * seizure disorder, history of cerebrovascular accident (CVA) or other serious neurological condition (e.g., Parkinson's disease, multiple sclerosis, seizure disorder \[except childhood febrile seizures\], dementia or delirium) * presence or history of neoplasia (other than resected non-melanotic skin cancer) * endocrinopathies (diabetes mellitus types I and II, Cushing's disease, Addison's disease) * active autoimmune disease (e.g., rheumatoid arthritis, Hashimoto's thyroiditis, inflammatory bowel disease) * chronic infection (e.g., hepatitis B or C or human immunodeficiency virus \[HIV\] infection) * acute kidney injury or Chronic Kidney Disease * any history of or current diagnosis of thrombosis or thrombophilia; if it is unclear whether a subject has received this diagnosis, a signed release will be obtained to contact the subject's treating physician and obtain accurate diagnostic information. Depending on the recommendation of the treating physician, the subject may undergo appropriate testing with the treating physician to verify the diagnosis, and if the tests produce negative findings, the subject may be allowed to enter the study. * any history of recurrent or recurring HSV (Herpes simplex) * any active enclosed infection (e.g., dental abscess, joint infection) * hemophilia or other cause for excessive bleeding (e.g., platelet disorder) * fever (Temp \> 99) of unknown origin at the time of screen * laboratory evidence of undiagnosed hypothyroidism or any change in treatment for hypothyroidism in the 3 months prior to screening. * significant electrocardiogram abnormalities * plan to receive surgery or medical procedure during the study * those with impaired sensation (e.g. diabetic polyneuropathy) * those with a deteriorated ability to express themselves * those in whom irradiating cold tissue, tissue badly supplied with blood or an area with low subcutaneous tissue (e.g. tibial border) 2. Any other medical condition that in the judgment of the PI would increase the risk of study participation or introduce excessive physiological variance into the study population 3. A positive score to C-SSRS items 4 or 5 is OR a suicide attempt in the past 12 months 4. Morbid obesity and/or body shape that might increase the risk of cutaneous burning from the Heckel HT3000 hyperthermia device (because of truncal skin being too close to the infrared lights defined as 3 inches or less) 5. Breast implants (because these increase the risk of burning) 6. Known hypersensitivity to hyperthermia and/or infrared exposure 7. Evidence of sunburn at time of treatment intervention 8. Use of any medication that might impact thermoregulatory capacity within 5 days of receiving WBH treatment, including: stimulants, diuretics, barbiturates, beta-blockers, antipsychotic agents, anti-cholinergic agents or chronic use of antihistamines, aspirin (other than low-dose ASA for prophylactic purposes), non-steroidal anti-inflammatory drugs (NSAIDs), systemic corticosteroids, cytokine antagonists 9. Use of any other medication that in the judgment of the PI would increase risk of study participation or introduce excessive variance into physiological or behavioral responses to WBH 10. Breastfeeding or pregnant women, women intending to become pregnant within 6 months of the screening visit, or sexually-active women of child bearing potential who are not using a medical accepted means of contraception (defined as oral contraceptive pill or implant, condom, diaphragm, IUD, status-post tubal ligation, or partner with vasectomy) 11. Any of the following exclusionary conditions for treatment with tocilizumab: * Taking immunosuppressive drugs including but not limited to: * Disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate * Corticosteroids such as prednisone * Monoclonal antibodies such as anti-CD20 monoclonal antibodies * Taking selective co-stimulation modulators * Regularly taking nonsteroid anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors in the 24 hours prior to WBH treatment and/or biomarker assessment * Absolute neutrophil count (ANC) below 2000 per mm3 or a history of neutropenia * Platelet count below 100,000 per mm3 or a history of thrombocytopenia * Elevated ALT or AST levels above 1.5 times the upper limit of normal (ULN) * Known hypersensitivity to tocilizumab or other ingredients in ACTEMRA * History of tuberculosis (TB), past exposure to TB, positive TB test result, residence or travel to areas of endemic TB or endemic mycoses within previous 6 months, meets TB risk factors after evaluation * History of having received the Bacillus Calmette-Guérin (BCG) vaccine * Has an underlying condition that may predispose them to infection (e.g., HIV, autoimmune disorders, on chemotherapy, etc) * Has a history of or an increased risk for gastrointestinal perforation such as a history of diverticulitis, stomach or intestinal ulcers or abdominal pain that does not go away * History of demyelinating disorders such as multiple sclerosis or chronic inflammatory demyelinating polyneuropathy * Have received a live vaccination in the one month prior to the scheduled administration of tocilizumab 12. A lifetime history of any Psychotic Disorder, bipolar I or II disorder, anorexia nervosa 13. Meeting DSM-5 criteria at screening for current obsessive compulsive disorder or bulimia nervosa. 14. Patients who have failed to respond during the course of their current major depressive episode to \>4 adequate antidepressant trials, defined as six weeks or more of treatment with the FDA-defined minimally effective dose, as assessed by the ATRQ. 15. A concurrent anxiety disorder (e.g., obsessive compulsive disorder, panic disorder, posttraumatic stress disorder) that appears to be an individual's primary clinical problem (with the result that depressive symptoms are judged to either result from this primary condition or to be secondary to it) 16. A concurrent personality disorder (e.g., borderline personality disorder, narcissistic personality disorder, histrionic personality disorder) that appears to be an individual's primary clinical problem (with the result that depressive symptoms are judged to either result from this primary condition or to be secondary to it) 17. Meets criteria for any substance use disorder in 3 months previous to screening (except for nicotine or caffeine use disorder) 18. Lifetime history of antisocial personality disorder 19. Use of antidepressant or other psychotropic medications (other than benzodiazepine or non-benzodiazepine sleeping aids, e.g., zolpidem at a stable dose for at least 4 weeks) within 4 weeks of screening (8 weeks for fluoxetine due to its extended half-life) 20. Participation in ongoing psychotherapy unless it has been stable for at least 3 months and individual has not improved (i.e., still meets criteria for MDD per MINI) 21. Commencement of any psychotropic or psychotherapeutic intervention between screening and study completion 22. A score of 4 or 5 on the Columbia Suicide Rating Scale (C-SSRS), consistent with active suicidal ideation with specific plan and intent, or suicide attempt within 12 months of screening per self-report 23. Claustrophobia of sufficient severity to interfere with ability to enter/remain in Heckel HT3000 device